Aquaculture research in recent times has been focused on finding more affordable sources of plant protein for inclusion in the fish diet. Lemna minor is a widely reported alternative protein source in fish feed but its effect on the immune system of fish especially catfish is not yet fully understood. This study, therefore, evaluated the effect of dietary inclusion of L. minor on the growth, immune response and catalase activity of Heteropneustes fossilis. The fry of H. fossilis was fed five iso-nitrogenous diets containing graded percentage inclusion levels of L. minor as 0% (Control), 5% (T1), 10% (T2), 15% (T3) and 20% (T4) for 60 days. The final weight, body mass gain and specific growth rate were significantly higher in T3 diet-fed fish than in others.The feed conversion ratio was lowest in the T3 group. Total muscle protein, mucus protein and total immunoglobulin content did not differ significantly between the control group and plant-fed fish. The lysozyme and alkaline phosphatase activity was significantly higher in T1. Antioxidant enzyme catalase activity did not differ significantly in all the treatments. This study shows that L. minor can be incorporated up to 20% in the feed of H. fossilis without a negative effect on its growth and immune response of H. fossilis. L. minor may be a potential protein source in fish feed for sustainable aquaculture.