The pricing of conventional feed ingredients used in aquaculture have become prohibitive, necessitating the need for locally sourced and cheaper alternatives that will promote fish production at competitive price. Thus, this study evaluated the suitability of fermented cassava leaf meal (FCLM) as substitute for soybean meal (SBM) in the diets for all-male Oreochromis niloticus fingerlings. Cassava leaf meal (CLM) was collected as a crop residue after harvesting cassava tuber and fermented with Chaetomium globosum (MTCC-4179) at concentration of 3 × 105 cell/g for 144 h. The nutritional and antinutritional composition of CLM relative to that of FCLM was assessed. Four isonitrogenous (35% crude protein) and iso-energetic (18.53 kJ/g) diets in which FCLM replaced SBM at 0 (FCLM0), 100 (FCLM100), 200 (FCLM200), and 300 g/kg (FCLM300) were prepared. The diets were fed to all-male O. niloticus fingerlings (average weight, 6.21 ± 0.05 g) for 60 days in a completely randomized experimental design after which their growth performance and haemato-biochemistry were evaluated. Fermentation increased the crude protein, total essential and non-essential amino acid contents of CLM. The crude fibre, tannin and cyanide contents were degraded by 20%, 43% and 17%, respectively. Growth performance in the group that received FCLM100 and FCLM200 was statistically comparable (p > 0.05) to the group reared on control (FCLM0). FCLM300 significantly depressed the growth parameters relative to other dietary groups (p < 0.05). Significantly lower PCV (27.00 ± 0.50%), haemoglobin (6.75 ± 0.25 g/dL) and serum total protein (2.51 ± 0.19 g/dL) were observed in FCLM300-fed group compared with other dietary groups (p < 0.05). When compared to the other groups, the group fed with FCLM300 had significantly higher serum glucose levels (p < 0.05). However, the red blood cells (RBC), white blood cells (WBC), lymphocyte, triglycerides, high-density lipoprotein and low-density lipoprotein contents of the fish in the different experimental groups were similar (p > 0.05). The present study demonstrated the possibility of replacing 200 g/kg SBM with FCLM without compromising growth and health status of all-male O. niloticus fingerlings.