The non-invasive Nexfin cardiac output (CO) monitor shows a low level of agreement with the gold standard thermodilution method in morbidly obese patients. Here we investigate whether this disagreement is related to excessive bodyweight, and can be improved when bodyweight derivatives are used instead. We performed offline analyses of cardiac output recordings of patient data previously used and partly published in an earlier study by our group. In 30 morbidly obese patients (BMI > 35 kg/m2) undergoing laparoscopic gastric bypass, cardiac output was simultaneously determined with PiCCO thermodilution and Nexfin pulse-contour method. We investigated if agreement of Nexfin-derived CO with thermodilution CO improved when ideal and adjusted—instead of actual- bodyweight were used as input to the Nexfin. Bodyweight correlated with the difference between Nexfin-derived and thermodilution-derived CO (r = −0.56; p = 0.001). Bland Altman analysis of agreement between Nexfin and thermodilution-derived CO revealed a bias of 0.4 ± 1.6 with limits of agreement (LOA) from −2.6 to 3.5 L min when actual bodyweight was used. Bias was −0.6 ± 1.4 and LOA ranged from −3.4 to 2.3 L min when ideal bodyweight was used. With adjusted bodyweight, bias improved to 0.04 ± 1.4 with LOA from −2.8 to 2.9 L min. Our study shows that agreement of the Nexfin-derived with invasive CO measurements in morbidly obese patients is influenced by body weight, suggesting that Nexfin CO measurements in patients with a BMI above 35 kg/m2 should be interpreted with caution. Using adjusted body weight in the Nexfin CO-trek algorithm reduced the bias.