Female-biased mortality has been consistently reported in Pacific salmon during their adult upriver migration. We collected coho salmon ( Oncorhynchus kisutch (Walbaum, 1792)) upon arrival at their spawning grounds to test whether females are more prone to cardiac oxygen limitations following exercise stress. We used a surgical approach to periodically sample arterial and venous blood over 48 h following recovery from a chase protocol to induce maximum metabolic rate. We found no significant differences in arterial or venous partial pressures of O2 between males and females. Female salmon had significantly elevated plasma cortisol levels but there were no effects of sex on either plasma lactate or K+. Our data show that female coho salmon do not suffer oxygen limitations to the spongy myocardium after a single exercise event at moderate temperatures (14 °C)—at least not when arriving to their spawning grounds. This study found no clear support for a cardiac oxygen limitation underlying elevated female mortality in Pacific salmon. Neither, however, does our study design nor specific findings allow us to rule out cardiac limitations in these fish. Future work should address whether potential oxygen limitations to the spongy myocardium at high temperatures or oxygen limitations to the compact myocardium via coronary blood flow contribute to female-biased mortality earlier on the migratory route.