Total mercury and fatty acids contents were determined in muscles of croaker, snapper, dolphinfish, blue marlin, and shark, from different markets in the Metropolitan District of Quito, Ecuador. Fifty-five samples were collected and analyzed for total mercury using cold vapor atomic fluorescence spectrometry, and the fatty acids were analyzed using gas chromatography equipped with a flame ionization detector. The lowest total mercury levels were found in snapper [0.041 µg·g wet weight (ww)] while blue marlin showed the highest (5.883 µg·g ww). EPA + DHA ranged from 1.0 mg·g in snapper to 2.4 mg·g in shark. A high omega-3/omega-6 ratio was found for all fish types; however, the HQ for the benefit-risk ratio was above 1, suggesting an evident risk to human health. Based on our results, consumption of croaker and dolphinfish is recommended up to one serving per week, considering the importance of EFAs intake and avoiding fish with elevated MeHg content. Therefore, Ecuadorian authorities could enhance public standards for seafood safety and develop consumer advice for pregnant women and young children to determine good fish choices or those to avoid.