Abstract Background It remains debated how much fluid should be administered during surgery. The atrial natriuretic peptide precursor proANP is released by atrial distension and deviations in plasma proANP are reported associated with perioperative fluid balance. We hypothesized that plasma proANP would decrease when the central blood volume is compromised during the abdominal part of robot-assisted hybrid (RE) esophagectomy and that a positive fluid balance would be required to maintain plasma proANP. Methods Patients undergoing RE ( n = 25) or open (OE; n = 25) esophagectomy for gastroesophageal cancer were included consecutively in this prospective observational study. Plasma proANP was determined repetitively during esophagectomy to allow for distinction between the abdominal and thoracic part of the procedure. The RE group was 15° head up tilted during the abdominal procedure. Results The blood loss was 250 (150–375) (RE) and 600 ml (390–855) (OE) ( p = 0.01), but the two groups of patients were provided with a similar positive fluid balance: 1705 (1390–1983) vs. 1528 ml (1316–1834) ( p = 0.4). However, plasma proANP decreased by 21% ( p