Various embodiments disclosed herein relate to detecting leaks in a patient monitoring system. The system can include a fluid handling network configured to receive a fluid sample drawn from a patient and to deliver at least a portion of the fluid sample to an analyte measurement system. The system can isolate at least a portion of the fluid handling network, can apply pressure to the at least a portion of the fluid handling network, can measure the pressure in the at least a portion of the fluid handling network, and can determine whether a leak is present in the at least a portion of the fluid handling network based at least in part on the measured pressure.