This study evaluated the growth performance, haematological indices, and biochemical parameters of four catfish breeds, including two purebreds (Clarias cavernicola and Clarias gariepinus) and two hybrids (female C. cavernicola x male C. gariepinus and female C. gariepinus x male C. cavernicola). Over four months, growth was assessed by measuring body weight, total length, and standard length. Haematological and biochemical analyses were conducted to assess the health and immune status of the different breeds. The results indicated that the hybrid of female C. cavernicola x male C. gariepinus exhibited the highest growth performance, with significant increases in body weight and length compared to the other breeds. This hybrid also demonstrated the highest white blood cell (WBC) and lymphocyte counts, suggesting a stronger immune response, which was statistically significant (p<0.05) compared to the purebreds. Granulocyte levels were consistent across all breeds, while red blood cell (RBC) and platelet counts showed no significant differences, indicating stability in these parameters. Biochemical analysis revealed that the female C. cavernicola x male C. gariepinus hybrid had the highest total protein and globulin levels, which are indicative of better health and immune function. Albumin levels were higher in both hybrids compared to the purebreds, while cholesterol, creatinine, and glucose levels were similar across all breeds. The alleles associated with better immunity are likely present in the maternal line of C. cavernicola, leading to the superior vigour observed in the C. cavernicola (female) x C. gariepinus (male) hybrid. This enhanced vigour results in improved growth, hematological, and biochemical profiles. Compared to purebred breeds, this hybrid demonstrates better health, increased disease resistance, and a higher potential for productivity in aquaculture.