Clarias gariepinus (African catfish) and Oreochromis niloticus (Tilapia fish) from the right North bank of the Senegal River in Mauritania (Rosso, Boghé, and Kaédi) were sampled during 1-year monitoring and tested for lead (Pb), cadmium (Cd), and mercury (Hg) levels. Fishing from the Senegal River is an essential source of food for the local population and these two species are the most common. Muscle presents higher Hg concentrations than liver and gills for both species. Gill Hg concentrations from Kaédi are higher than Boghé and Rosso for both species. The Cd levels measured in gills were low in the different locations and revealed high variation throughout the 1-year study. No significant differences were observed between concentrations of Cd in Clarias gariepinus and Oreochromis niloticus parts. Statistical treatment did not show a considerable variation of Pb concentration between the different parts, revealing lower levels in gills from Boghé than the ones from Kaédi and Rosso. The associated human health risk was calculated from the concentration levels using the target hazard quotient (THQ) approach. Even though all the THQ values and the hazard index were lower than 1 for the determined trace metals when the exposure frequency was not greater than three times a week, eating frequency in the studied locations sometimes is greater than five, thus posing a health risk, especially at Kaédi and Boghé.