diff --git a/apollo-router/src/uplink/mod.rs b/apollo-router/src/uplink/mod.rs
index f9afb7ce49..8f10a44c28 100644
--- a/apollo-router/src/uplink/mod.rs
+++ b/apollo-router/src/uplink/mod.rs
@@ -1,3 +1,4 @@
+use std::error::Error as stdError;
 use std::fmt::Debug;
 use std::time::Duration;
 use std::time::Instant;
@@ -359,7 +360,27 @@ where
     Query: graphql_client::GraphQLQuery,
 {
     let client = reqwest::Client::builder().timeout(timeout).build()?;
-    let res = client.post(url).json(request_body).send().await?;
+    // It is possible that istio-proxy is re-configuring networking beneath us. If it is, we'll see an error something like this:
+    // level: "ERROR"
+    // message: "fetch failed from all endpoints"
+    // target: "apollo_router::router::event::schema"
+    // timestamp: "2023-08-01T10:40:28.831196Z"
+    // That's deeply confusing and very hard to debug. Let's try to help by printing out a helpful error message here
+    let res = client
+        .post(url)
+        .json(request_body)
+        .send()
+        .await
+        .map_err(|e| {
+            if let Some(hyper_err) = e.source() {
+                if let Some(os_err) = hyper_err.source() {
+                    if os_err.to_string().contains("tcp connect error: Cannot assign requested address (os error 99)") {
+                        tracing::warn!("If your router is executing within a kubernetes pod, this failure may be caused by istio-proxy injection. See https://github.com/apollographql/router/issues/3533 for more details about how to solve this");
+                    }
+                }
+            }
+            e
+        })?;
     tracing::debug!("uplink response {:?}", res);
     let response_body: graphql_client::Response<Query::ResponseData> = res.json().await?;
     Ok(response_body)