Background: Cerebral oximetry using near-infrared spectroscopy (NIRS) is used for monitoring cerebral oxygen saturation during cardiac surgery and is correlated with clinical outcomes. Our goal was to explore cerebral and somatic NIRS in liver resections as a predictor of post-operative complications. Methods: Prospective observational and non-interventional study from a tertiary care university hospital including adult patients undergoing liver resection monitored using NIRS at four sites before and during surgery. Those sites were: frontotemporal left and right zones, right thigh, and right arm. Anesthesiologists and surgeons were blinded to oximetry values. Correlations were assessed between baseline oximetry values and cerebro-somatic desaturation load (threshold of 80% from baseline) values with peri-operative events and complications. Results: Ninety patients were distributed equally among gender with a mean age of 59.7 ± 13.1 years. Lower baseline cerebral and/or somatic values were associated with increased risk of delirium, respiratory failure, surgical and renal complications, blood transfusions, and length of stay in the intensive care unit and in the hospital (P < 0.05). The severity of somatic desaturation below 80% was the only parameter associated with blood losses (P = 0.030) and length of hospital stay (P = 0.047). Conclusions Cerebral and somatic desaturation does occur in liver resection and can be used simultaneously during liver surgery. Both baseline cerebral and somatic NIRS values are correlated with complications and outcomes. However, thigh desaturation appears more sensitive than cerebral NIRS values in predicting some of these complications.