Lipid microdomains are microscopic portions of the cell membrane comprised of cholesterol, proteins, and sphingolipids. They are presumed to be responsible for cell signaling and transduction. Studies conducted show that cows supplemented with fish meal have decreased cell signaling related to prostaglandin F2α in the cells of their corpora lutea. Since fish meal is high in omega-3 fatty acids, it is postulated that the omega-3 fatty acids are affecting the cholesterol and sphingolipids in lipid microdomains. The objective of this research was to examine the effect of fish oils enriched with omega-3 fatty acids on distribution of lipid microdomain proteins flotillin and caveolin in bovine luteal cells. Mixed luteal cells from 4 bovine corpora lutea were prepared and incubated in T-75 flasks containing Ham’s F-12 medium with 5% fetal calf serum, insulin, transferrin (5 µg/ml), selenium (5 ng/ml), 100 U/ml penicillin, 0.1 mg/ml streptomycin, and 0.25 mg/ml amphotericin B in an atmosphere of humidified 95% air and 5% CO2 at 37°C. At confluence, cells were trypsinized and either10 mM of βMCD was added, 3 × 10-2 % fish oil was added or cells were left untreated (control). Control cells contained lipid microdomains with high fluorescent intensity while βMCD cells had a less intense fluorescent image and more dispersed microdomains. Fish oil treated cells showed similar results as the βMCD treated cells. In conclusion, fish oils containing omega-3 fatty acids may alter the lipid microdomains of bovine luteal cells thus altering the cell signaling pathway of prostaglandin F2α.