© 2018, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.Postoperative pain begins with tissue incision, continues with the production of free oxygen radicals, and is intensified by the inflammatory response. We investigated the effect of esomeprazole on postoperative pain and lung and heart complications of laparotomy. Albino Wistar-type rats were grouped into the paw scalpel incision (PSI), applied control (SIC), PSI + 20 mg/kg esomeprazole (SIE), PSI + 20 mg/kg meperidine (SIM), and healthy group (HG). For the laparotomy test, the rats were grouped as follows: laparotomy applied control (LTC), laparotomy + 20 mg/kg esomeprazole (LTE), laparotomy + 20 mg/kg meperidine (LTM), and healthy group (HG). Meperidine suppressed the PSI-induced pain. Esomeprazole decreased the level of oxidant and proinflammatory cytokines in the serum and lung and heart tissues of the LTE group and in the paw tissues of the SIE group, but meperidine did not. There were no histopathological findings in the lung and heart tissues of the LTE group, but tissue damage was found in the LTC and LTM groups. Esomeprazole may help reduce major surgery complications.