Background Water pollutants cause adverse efects in aquatic ecosystems. The immunomodulatory and mitigat‑ ing efects of dietary 1,3‑glucan on ipronil and lead‑induced intoxication in African catish (Clarias gariepinus) were investigated. Two hundred forty catish were randomly divided into four equal groups: those in the irst group were fed basic diet and served as controls; those in the second group were supplemented with β‑1,3‑glucan (0.1%); those in the third group were exposed to combination of lead nitrate at 0.041 mg/L (1/10 96 h LC50) and ipronil at 2.8 mg/l (1/10 96 h LC50); and those in the fourth group were exposed to combination of ipronil, lead, and β‑1,3‑glucan. The health status, haematological, immunological, and histological changes were all evaluated. Result Swelling on the dorsolateral side, spinal column deviation, sluggish movement, skin bleaching, excessive mucus secretion, signiicant variations in blood indices‑related measures, and a 45% death rate were observed in the third group. There was a signiicant reduction in interleukin‑1 (IL‑1) and interleukin‑6 (IL‑6) and immunoglobulin M (IgM) concentrations, as well as decrease in their corresponding gene expression, indicating that ipronil and lead had immunosuppressive activity. Severe catarrhal enteritis and mucinous degeneration of the lining epithelium, and notable depletion of white pulp, congested red pulp and hemosiderosis were common pathological indings in the spleen. β‑1,3‑glucan alone or in combination with ipronil and lead provoked physical activity, blood indices, with elevations in IL‑1β, IL‑2, IL‑6, and IgM concentrations, as well as up‑regulation in their genes’ expression in splenic tissues, when compared to the third group. The spleen and intestine had normal histological architecture with 5% mortalities. There were no ish deaths in the β‑1,3‑glucan‑alone or control groups. Conclusion The use of β‑1,3‑glucan (0.1%) as dietary supplement could be implemented to protect against the toxic efects of ipronil and lead toxicity by improving the health and immunological parameters of intoxicated catish.