Embodiments are directed towards managing persistence of network traffic using deep packet inspections of network response packets from an application server. In one embodiment, the network packets are associated with SIP messages. A traffic management device (TMD) interposed between client devices and a plurality of application servers receives messages from the client device and/or the application servers. The TMD performs a deep packet inspection to determine if a defined key value pair that includes a session identifier is detected. If so, and the message is from the application server, the session identifier is then mapped to an application server identifier to persistently refer each subsequent inbound packet from a client device having the same session identifier to the application server mapped to the session identifier.