We present an animal model used to evaluate the in vivo performance of electrochemical amperometric continuous lactate sensors compared to blood gas instruments. Electrochemical lactate sensors were fabricated, placed into 5 Fr central venous catheters (CVCs), and paired with wireless potentiostat devices. Following in vivo evaluation and calibration, sensors were placed within the jugular and femoral veins of a porcine subject as a preliminary assessment of in vivo measurement accuracy. The mobile electronic circuit potentiostat devices supplied the operational voltage for the sensors, measured the resultant steady-state current, and recorded the sensor response values in internal memory storages. An in vivo time trace of implanted intravenous (IV) sensors demonstrated lactate values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. Currents measured continuously from the implanted lactate sensors over 10 h were converted into lactate concentration values through use of a two-point in vivo calibration. Study shows that intravenously implanted sensors had more accurate readings, faster peak-reaching rates, and shorter peak-detection times compared to subcutaneously placed sensors. IV implanted and subcutaneously placed sensors closer to the upper body (in this case neck) showed faster response rates and more accurate measurements compared to those implanted in the lower portion of the porcine model. This study represents an important milestone not only towards continuous lactate monitoring for early diagnosis and intervention in neonatal patients with congenital heart disease undergoing cardiopulmonary bypass surgeries, but also in the intervention of critical ill patients in the Intensive Care Units or during complex surgical procedures.