Purpose Naltrexone (NTX) is an opioid antagonist that can reverse the physiological effects of opioid receptors when bound. Opioid receptors have been found to play a role in cardiovascular (CV) function, and thus, binding of NTX may alter CV activity at rest and in response to acute and chronic exercise (EX). We hypothesized that opioid receptor blockade will alter the typical CV responses following acute EX. Methods We assessed the effects of opioid receptor blockade on CV function via echocardiography in mice following an acute bout of forced swimming (FSw), a model of rodent EX. We administered opioid receptor antagonist, NTX, or saline in mice before FSw and in the absence of an FSw perturbation. Furthermore, we assessed how NTX can influence maximal EX capacity on a rodent treadmill. Results Our data shows that NTX administration does not decrease maximal EX capacity in mice (P > 0.05). However, NTX attenuated cardiac output following FSw (FSw = 52.5 ± 2.5 ml/min vs. FSw + NTX = 32.7 ± 5.2 ml/min; P < 0.05) when compared with saline control (33.5 ± 3.8 ml/min). Further, the administration of NTX in the non-EX condition significantly (P < 0.05) reduced ejection fraction. Conclusion These data suggest that normal opioid receptor activation is necessary for typical CV function following FSw.