Pacific Krill (Euphausia pacifica) are small, red crustaceans, similar to shrimp, that flourish in the North Pacific and are eaten in Japan. We investigated the effect of a water-soluble extract of Pacific Krill on adipocytes and discovered that this extract suppressed triglyceride accumulation in adipocytes. Furthermore, the water-soluble extract of Pacific Krill suppressed the expression of two master regulators of adipocyte differentiation, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα). C/EBPβ promotes PPARγ and C/EBPα expression, but the water-soluble extract of Pacific Krill did not inhibit the expression of C/EBPβ or C/EBPβ-mediated transcriptional activation. The Pacific Krill extract was more effective than a PPARγ antagonist in suppressing PPARγ and C/EBPα expression. These results indicated that the water-soluble extract of Pacific Krill was not simply a PPARγ antagonist, but that it prevented triglyceride accumulation in adipocytes by suppression of PPARγ and C/EBPα via a pathway that is independent of C/EBPβ.