Mounting evidence suggests that the benefits of fish consumption are not limited to the well-appreciated effects of omega-3 fatty acids. We previously demonstrated that cod protein protects against the development of diet-induced insulin resistance. The goal of this study was to determine whether other fish protein sources present similar beneficial effects. Rats were fed a high-fat, high-sucrose diet containing protein from casein or fish proteins from bonito, herring, mackerel, or salmon. After 28 days, oral glucose tolerance tests or hyperinsulinemic-euglycemic clamps were performed; and tissues and plasma were harvested for biochemical analyses. Despite equal energy intake among all groups, the salmon-protein–fed group presented significantly lower weight gain that was associated with reduced fat accrual in epididymal white adipose tissue. Although this reduction in visceral adiposity was not associated with improved glucose tolerance, we found that whole-body insulin sensitivity for glucose metabolism was improved using the very sensitive hyperinsulinemic-euglycemic clamp technique. Importantly, expression of both tumor necrosis factor– α and interleukin-6 was reduced in visceral adipose tissue of all fish-protein–fed groups when compared with the casein-fed control group, suggesting that fish proteins carry anti-inflammatory properties that may protect against obesity-linked metabolic complications. Interestingly, consumption of the salmon protein diet was also found to raise circulating salmon calcitonin levels, which may underlie the reduction of weight gain in these rats. These data suggest that not all fish protein sources exert the same beneficial properties on the metabolic syndrome, although anti-inflammatory actions appear to be common.