The effects of Harness® toxicity on fish health are little known. So, current work aimed to study the impact of sub-lethal doses of Harness® (an acetochlor-based herbicide) on the African catfish, Clarias gariepinus, and also investigated the potential role of lycopene (LYCO) administration in alleviating Harness® negative effects. Fish were divided into five groups in triplicates as follows: group 1 (control) received no treatment, group 2 was exposed to 10 μm Harness®/L, group 3 was orally administered 10 mg LYCO/kg body weight and exposed to 10 μm Harness®/L, group 4 was exposed to 100 μm Harness®/L, and group 5 was orally administered 10 mg LYCO/kg body weight and exposed to 100 μm Harness®/L for 2 weeks. Some hemato-biochemical parameters, genotoxicity, and histopathological changes were assessed at the end of this period. Sub-lethal doses of Harness® altered the shape of erythrocytes in contrast to the control sample. Also, hematological parameters of exposed fish exhibited a significant (P < 0.05) reduction in the values of red blood cell count (RBCs), hemoglobin (Hb), hematocrit (HCT), and platelets (PL), as well as an insignificant (P > 0.05) drop in mean corpuscular volume (MCV). Harness® was also found to cause genotoxicity as well as histopathological alterations. LYCO administration decreased hemato-biochemical changes and returned them to near-normal levels. The findings showed that LYCO administration (10 mg LYCO/kg body weight) decreased Harness® toxicity in C. gariepinus and alleviated its destructive effects.