Multiple studies of left ventricular dysfunction suggest that females may be more resistant to ischemia or endotoxemia. However, sex differences in right ventricular (RV) responses to pressure overload and/or endotoxemia have not been elucidated. We hypothesized that females would maintain better RV function during acute pressure overload (APO), endotoxemia, or a simultaneous insult from both processes. Age-matched male and proestrus female Sprague-Dawley rats were given an intraperitoneal injection of either phosphate buffered saline or LPS. Six hours after injection, hearts were removed by median sternotomy and isolated via Langendorff. End-diastolic pressures were sequentially elevated past physiologic levels by increasing the volume of a latex balloon that was inserted into the RV. Male RV function was depressed to a greater degree after APO injury compared with that in females (developed pressure: male, 44.97 mmHg vs. female, 58.23 mmHg). Interestingly though, at a physiologic end-diastolic pressure of 5 mmHg, endotoxic males and females maintained equivalent RV function. However, with concurrent endotoxic insult and APO, RV function was better maintained in males as compared with that in females (developed pressure: male, 59% of control versus female, 41% of control). Furthermore, tissue levels of IL-1 and IL-6, but not IL-10, were increased after endotoxin exposure but did not differ based on sex. Through this study, we have shown that sex differences exist in RV dysfunction, and that different cardiac insults diversely affect myocardial function. Understanding these differences may allow for the implementation of novel therapeutic treatment options that are designed to attenuate RV cardiovascular collapse.