Arsenic (As) and mercury (Hg) concentrations in the sediment and tissues of Oreochromis niloticus fish from a Nile River canal (Muweis Canal), Egypt, were subjected to an investigation between May and July 2022 at six stations along the canal. Concentrations of As and Hg were determined via an atomic absorption spectrophotometer. The results showed that the concentrations of metals in the liver, muscle and sediment varied significantly among the different sampling sites. The contamination factor (CF) and potential ecological risk index (RI) indicated a considerable risk for aquatic life. For O. niloticus consumption, the estimated daily intake (EDI) of Hg was less than the permissible daily intake.  However, the target hazard quotient (THQ) and target cancer risk (CR) values for As exceed the acceptable value range, suggesting a risk of cancer for consumers. Therefore, the continuous monitoring for heavy metals in Muweis Canal and similar localities in Egypt should be improved to preserve ecological and human health.