Continuous monitoring of blood parameters at the bedside is crucial for critically ill patients. Miniaturized biosensors integrated into medical devices in direct contact with blood can improve the quality of monitoring by reducing response time in emergencies as well as the invasiveness and blood consumption during the measurements. In such settings, coating biosensors with hemocompatible materials is essential for achieving biocompatibility and maximum acceptance of the devices for direct measurements of blood parameters in the human body. Here, we present an instrumented catheter equipped with a hemocompatible electrochemical sensor to continuously monitor one of the key parameters- glucose, lactate, and pH, directly in blood. Selective amperometric and potentiometric sensors were obtained by modifying the electrodes with enzymes and pH-responsive toluidine blue O. The glucose sensors exhibited a linear response from 0.06 to 10 mM with a sensitivity of −116 ± 16 nA/mMGlucose, while the lactate sensor had a linear response between 5 and 20 mM with a sensitivity of −38 ± 6 nA/mMLactate. A pH sensitivity of −20.17 ± 2.37 mV/pH for sensors with the hydrogel-covered TBO film has been reached. Hemocompatible properties, crucial for in vivo applications, were achieved by coating the functional electrode surfaces with an additional hydrogel layer based on a four-armed poly(ethylene glycol), cross-linked with the anticoagulant polysaccharide heparin. Initially, the functionalization strategy was thoroughly evaluated in terms of sensor response and hemocompatibility in a planar format; followed by a proof-of-principle demonstration of glucose sensing with a catheter imprinted with the respective electrochemical sensor.