diff --git a/instrumentation/opentelemetry-instrumentation-pymemcache/src/opentelemetry/instrumentation/pymemcache/package.py b/instrumentation/opentelemetry-instrumentation-pymemcache/src/opentelemetry/instrumentation/pymemcache/package.py
index 7229a3ba47..a75a6670ba 100644
--- a/instrumentation/opentelemetry-instrumentation-pymemcache/src/opentelemetry/instrumentation/pymemcache/package.py
+++ b/instrumentation/opentelemetry-instrumentation-pymemcache/src/opentelemetry/instrumentation/pymemcache/package.py
@@ -13,4 +13,4 @@
 # limitations under the License.
 
 
-_instruments = ("pymemcache >= 1.3.5, < 4",)
+_instruments = ("pymemcache >= 1.3.5, < 5",)
diff --git a/tox.ini b/tox.ini
index ec5589744d..5e4c62c6b0 100644
--- a/tox.ini
+++ b/tox.ini
@@ -122,8 +122,8 @@ envlist =
     ; ext-psycopg2 intentionally excluded from pypy3
 
     ; opentelemetry-instrumentation-pymemcache
-    py3{7,8,9,10,11}-test-instrumentation-pymemcache{135,200,300,342}
-    pypy3-test-instrumentation-pymemcache{135,200,300,342}
+    py3{7,8,9,10,11}-test-instrumentation-pymemcache{135,200,300,342,400}
+    pypy3-test-instrumentation-pymemcache{135,200,300,342,400}
 
     ; opentelemetry-instrumentation-pymongo
     py3{7,8,9,10,11}-test-instrumentation-pymongo
@@ -267,6 +267,7 @@ deps =
   pymemcache200: pymemcache >2.0.0,<3.0.0
   pymemcache300: pymemcache >3.0.0,<3.4.2
   pymemcache342: pymemcache ==3.4.2
+  pymemcache400: pymemcache ==4.0.0
   httpx18: httpx>=0.18.0,<0.19.0
   httpx18: respx~=0.17.0
   httpx21: httpx>=0.19.0
@@ -390,7 +391,7 @@ commands_pre =
 
   mysql: pip install {toxinidir}/instrumentation/opentelemetry-instrumentation-dbapi {toxinidir}/instrumentation/opentelemetry-instrumentation-mysql[test]
 
-  pymemcache{135,200,300,342}: pip install {toxinidir}/instrumentation/opentelemetry-instrumentation-pymemcache[test]
+  pymemcache{135,200,300,342,400}: pip install {toxinidir}/instrumentation/opentelemetry-instrumentation-pymemcache[test]
 
   pymongo: pip install {toxinidir}/instrumentation/opentelemetry-instrumentation-pymongo[test]