diff --git a/newsfragments/3440.feature.rst b/newsfragments/3440.feature.rst
new file mode 100644
index 0000000000..0693febdcc
--- /dev/null
+++ b/newsfragments/3440.feature.rst
@@ -0,0 +1 @@
+Implement a ``RequestTimedOut`` exception, extending from ``Web3RPCError``, for when requests to the node time out.
diff --git a/newsfragments/3440.internal.rst b/newsfragments/3440.internal.rst
new file mode 100644
index 0000000000..311ff918a2
--- /dev/null
+++ b/newsfragments/3440.internal.rst
@@ -0,0 +1 @@
+Mitigate inconsistently failing tests for CI runs with appropriate ``flaky`` or ``pytest.mark.xfail()`` decorators.
diff --git a/tests/core/manager/test_response_formatters.py b/tests/core/manager/test_response_formatters.py
index e906e5170a..331d25ceca 100644
--- a/tests/core/manager/test_response_formatters.py
+++ b/tests/core/manager/test_response_formatters.py
@@ -16,6 +16,7 @@
     BlockNotFound,
     ContractLogicError,
     MethodUnavailable,
+    RequestTimedOut,
     TransactionNotFound,
     Web3RPCError,
 )
@@ -77,6 +78,10 @@
     VALID_ERROR_RESPONSE,
     {"error": {"code": -32601, "message": (METHOD_UNAVAILABLE_MSG)}},
 )
+ERROR_RESPONSE_REQUEST_TIMED_OUT = merge(
+    VALID_ERROR_RESPONSE,
+    {"error": {"code": -32002, "message": "Request timed out."}},
+)
 ERROR_RESPONSE_INVALID_ID = merge(VALID_ERROR_RESPONSE, {"id": b"invalid"})
 
 ERROR_RESPONSE_INVALID_CODE = merge(VALID_ERROR_RESPONSE, {"error": {"code": "-32601"}})
@@ -190,6 +195,11 @@ def test_formatted_response_invalid_response_object(w3, response, error, error_m
             MethodUnavailable,
             METHOD_UNAVAILABLE_MSG,
         ),
+        (
+            ERROR_RESPONSE_REQUEST_TIMED_OUT,
+            RequestTimedOut,
+            f'{ERROR_RESPONSE_REQUEST_TIMED_OUT["error"]}',
+        ),
     ),
 )
 def test_formatted_response_valid_error_object(response, w3, error, error_message):
diff --git a/web3/_utils/module_testing/eth_module.py b/web3/_utils/module_testing/eth_module.py
index bb25e192a9..3432c0c3f4 100644
--- a/web3/_utils/module_testing/eth_module.py
+++ b/web3/_utils/module_testing/eth_module.py
@@ -76,6 +76,7 @@
     MultipleFailedRequests,
     NameNotFound,
     OffchainLookup,
+    RequestTimedOut,
     TimeExhausted,
     TooManyRequests,
     TransactionNotFound,
@@ -2359,7 +2360,9 @@ async def test_async_eth_replace_transaction_gas_price_too_low(
             await async_w3.eth.replace_transaction(txn_hash, txn_params)
 
     @pytest.mark.xfail(
-        reason="Very flaky on CI runs, hard to reproduce locally", strict=False
+        reason="Very flaky on CI runs, hard to reproduce locally",
+        strict=False,
+        raises=(RequestTimedOut, asyncio.TimeoutError, Web3ValueError),
     )
     @pytest.mark.asyncio
     async def test_async_eth_replace_transaction_gas_price_defaulting_minimum(
@@ -2385,7 +2388,9 @@ async def test_async_eth_replace_transaction_gas_price_defaulting_minimum(
         )  # minimum gas price
 
     @pytest.mark.xfail(
-        reason="Very flaky on CI runs, hard to reproduce locally", strict=False
+        reason="Very flaky on CI runs, hard to reproduce locally",
+        strict=False,
+        raises=(RequestTimedOut, asyncio.TimeoutError, Web3ValueError),
     )
     @pytest.mark.asyncio
     async def test_async_eth_replace_transaction_gas_price_defaulting_strategy_higher(
@@ -2416,7 +2421,9 @@ def higher_gas_price_strategy(async_w3: "AsyncWeb3", txn: TxParams) -> Wei:
         async_w3.eth.set_gas_price_strategy(None)  # reset strategy
 
     @pytest.mark.xfail(
-        reason="Very flaky on CI runs, hard to reproduce locally", strict=False
+        reason="Very flaky on CI runs, hard to reproduce locally",
+        strict=False,
+        raises=(RequestTimedOut, asyncio.TimeoutError, Web3ValueError),
     )
     @pytest.mark.asyncio
     async def test_async_eth_replace_transaction_gas_price_defaulting_strategy_lower(
diff --git a/web3/exceptions.py b/web3/exceptions.py
index 6b62b7fd2a..2ffe290de4 100644
--- a/web3/exceptions.py
+++ b/web3/exceptions.py
@@ -364,6 +364,12 @@ class MethodUnavailable(Web3RPCError):
     """
 
 
+class RequestTimedOut(Web3RPCError):
+    """
+    Raised when a request to the node times out.
+    """
+
+
 class TransactionNotFound(Web3RPCError):
     """
     Raised when a tx hash used to look up a tx in a jsonrpc call cannot be found.
diff --git a/web3/manager.py b/web3/manager.py
index f85e83adac..0a980ee1d3 100644
--- a/web3/manager.py
+++ b/web3/manager.py
@@ -37,6 +37,7 @@
     BadResponseFormat,
     MethodUnavailable,
     ProviderConnectionError,
+    RequestTimedOut,
     TaskNotRunning,
     Web3RPCError,
     Web3TypeError,
@@ -89,6 +90,13 @@
 
 
 NULL_RESPONSES = [None, HexBytes("0x"), "0x"]
+KNOWN_REQUEST_TIMEOUT_MESSAGING = {
+    # Note: It's important to be very explicit here and not too broad. We don't want
+    # to accidentally catch a message that is not for a request timeout. In the worst
+    # case, we raise something more generic like `Web3RPCError`. JSON-RPC unfortunately
+    # has not standardized error codes for request timeouts.
+    "request timed out",  # go-ethereum
+}
 METHOD_NOT_FOUND = -32601
 
 
@@ -185,6 +193,7 @@ def _validate_response(
             response, 'Response must include either "error" or "result".'
         )
     elif "error" in response:
+        web3_rpc_error: Optional[Web3RPCError] = None
         error = response["error"]
 
         # raise the error when the value is a string
@@ -202,7 +211,7 @@ def _validate_response(
                 response, 'error["code"] is required and must be an integer value.'
             )
         elif code == METHOD_NOT_FOUND:
-            exception = MethodUnavailable(
+            web3_rpc_error = MethodUnavailable(
                 repr(error),
                 rpc_response=response,
                 user_message=(
@@ -211,9 +220,6 @@ def _validate_response(
                     "currently enabled."
                 ),
             )
-            logger.error(exception.user_message)
-            logger.debug(f"RPC error response: {response}")
-            raise exception
 
         # errors must include a message
         error_message = error.get("message")
@@ -222,9 +228,26 @@ def _validate_response(
                 response, 'error["message"] is required and must be a string value.'
             )
 
-        apply_error_formatters(error_formatters, response)
+        if any(
+            # parse specific timeout messages
+            timeout_str in error_message.lower()
+            for timeout_str in KNOWN_REQUEST_TIMEOUT_MESSAGING
+        ):
+            web3_rpc_error = RequestTimedOut(
+                repr(error),
+                rpc_response=response,
+                user_message=(
+                    "The request timed out. Check the connection to your node and "
+                    "try again."
+                ),
+            )
+
+        if web3_rpc_error is None:
+            # if no condition was met above, raise a more generic `Web3RPCError`
+            web3_rpc_error = Web3RPCError(repr(error), rpc_response=response)
+
+        response = apply_error_formatters(error_formatters, response)
 
-        web3_rpc_error = Web3RPCError(repr(error), rpc_response=response)
         logger.error(web3_rpc_error.user_message)
         logger.debug(f"RPC error response: {response}")
         raise web3_rpc_error