The effect of the inclusion of Mytilus edulis shell collected from the Lagos Lagoon front, University of Lagos, in diets of Nile tilapia (Oreochromis niloticus) on the haematology of the fish was investigated in the Marine Research Laboratory of the University. Ten fingerlings each of O. niloticus were placed in plastic tanks and fed for 12 weeks with feed containing milled M. edulis shell substituted for Di-calcium phosphate (DCP), in other to utilize locally available and abundant non-conventional food materials. The substitutions were at the rate of 100% (T4), 75% (T3), 50% (T2), 25% (T1) and 0% (T0) the control diet. Each feeding regime was in triplicates. The mean water parameters during experimental period were within the normal range for tropical fishes, and were: mean temperature (27.78±0.57 - 28.17±0.57°C); pH (4±0.07 - 7.49±0.10) and dissolved oxygen (6.19±0.633 - 6.46±0.633mg/l). The proximate analysis of M. edulis shell showed higher crude protein content compared to DCP; this probably had a positive effect on the growth of the fish fed M. edulis shell. Fish fed with M. edulis shell showed a remarkable significant decrease (P>0.05) amongst diet in haematological parameters (Hb, WBC and RBC). However, the PCV values was highest in T3 (0.363±0.465) and lowest in the control diet (T0) (0.133±0.015). In conclusion, 75% level of substitution of Di-calcium phosphate with M. edulis shell in the diet O. niloticus yielded a better haematological parameter.