While it is well known that O2 is directly removed from the water by skin and gill tissues of fish, the mismatch between O2 removal from water (O2 uptake; [Formula: see text]) and the O2 delivered to tissues by the primary circulation (O2 consumption; [Formula: see text]) has never been measured directly. Using data from four recent studies that simultaneously measured [Formula: see text] and [Formula: see text] in 2-5 kg Pacific salmon, our analysis revealed that sockeye salmon can remove an additional 12-48 % more O2 from the water than the primary circulation delivers to the systemic tissues. This percentage did not change significantly during swimming activity, a result that contradicts an earlier prediction that the difference should decrease when [Formula: see text] increases during exercise. In resting Chinook salmon, a similar percentage difference in simultaneously measured [Formula: see text] and [Formula: see text] was observed, yet the difference tended to disappear during acute heat stress to a near lethal temperature. These results emphasize that caution should be exercised when using the Fick equation to estimate cardiac output because the overestimate of cardiac output that results from using the Fick equation in Pacific salmon is not small, may not be fixed and may exist in other teleosts.