Previous studies have shown that fish protein, as well as marine n-3 PUFA, may have beneficial effects on cardiovascular risk profile. The objectives of this study were to investigate the combined effects of fish gelatine (FG) and n-3 PUFA supplementation on (1) energy intake and body weight, (2) lipid profile and (3) inflammatory and CVD markers in free-living insulin-resistant males and females. Subjects were asked to consume, in a crossover study design with two experimental periods of 8 weeks each, an n-3 PUFA supplement and n-3 PUFA supplement plus FG (n-3 PUFA + FG). n-3 PUFA + FG led to an increase in protein intake and a decrease in carbohydrate intake compared with n-3 PUFA (P < 0·02) in males and females. Sex–treatment interactions were observed for TAG (P = 0·03) and highly sensitive C-reactive protein (hsCRP) (P = 0·001) levels. In females, n-3 PUFA reduced plasma TAG by 8 % and n-3 PUFA + FG by 23 %, whereas in males, n-3 PUFA reduced plasma TAG by 25 % and n-3 PUFA + FG by 11 %. n-3 PUFA increased serum hsCRP by 13 % and n-3 PUFA + FG strongly reduced hsCRP by 40 % in males, whereas in females, n-3 PUFA reduced serum hsCRP by 6 % and n-3 PUFA + FG increased hsCRP by 20 %. In conclusion, supplementation with FG may enhance the lipid-lowering effect of marine n-3 PUFA in females and beneficially counteract the effect of n-3 PUFA on serum hsCRP in males. Further studies are needed to identify the sex-dependent mechanisms responsible for the divergent effects of FG on TAG and hsCRP levels in females and males, respectively.