Sepsis is a severe inflammatory response to systemic infection that frequently affects the myocardium. Previous studies have suggested that resveratrol (RESV) is protective in sepsis. The present study aimed to investigate the role of sirtuin 1 (Sirt1) signaling in the protective effect of intraperitoneally administered RESV against sepsis‑induced myocardial injury. Cecal ligation and puncture, or a sham operation, were performed in male Sprague‑Dawley rats, and the levels of tumor necrosis factor (TNF)‑α and myeloperoxidase (MPO) were assessed by ELISA and an MPO activity kit, respectively. The extent of myocardial apoptosis was assessed by TUNEL staining. The protein expression levels of Sirt1, acetylated (Ac)‑Forkhead box O1 (FoxO1), B cell lymphoma 2 apoptosis regulator (Bcl‑2) and Bcl‑2 associated protein X apoptosis regulator (Bax) were detected by western blot analysis. RESV was demonstrated to attenuate myocardial apoptosis and decrease the production of TNF‑α and MPO. Additionally, RESV upregulated the expression of Sirt1 and Bcl‑2, and downregulated the expression of Ac‑FoxO1 and Bax. The protective effects of RESV were abolished by EX527, a Sirt1 inhibitor. RESV has therefore been demonstrated to attenuate myocardial injury in sepsis by decreasing neutrophil accumulation, TNF‑α expression, and myocardial apoptosis via activation of Sirt1 signaling. These results suggest a novel therapeutic strategy for the clinical treatment of sepsis.