A total number of 135 Nile tilapia (O. niloticus) were used to study the effect of dietary supplementation with black cumin seed (Nigella sativa) on growth performance and some blood constituents. The fish were randomly divided into three treatment groups each of 45 fish, and each group was divided into 3 subgroups (15 fish / unit). These groups received N. sativa at 1% (T1) and 2% (T2) and control group (C) which fed on basal diet without N. sativa. Body weight and length were recorded biweekly all over the experimental period (12 weeks). Blood samples from each fish were collected to determine each of hemoglobin (Hb), packed cell volume (PCV%), serum glucose, total protein, albumin, globulin, and alkaline phosphatase. Ten fish were scarified to determine hepatosmatic index (HSI), spleen somatic index (SSI), and gonadosomatic index (GSI). Other ten fish were transported to wet laboratory and reared without oxygen supplementation to determine the resistance under oxygen deficiency. The results showed that there was insignificant increase in body weight, body weight gain, total length, and length increment in T2. Also, the hemoglobin increased insignificantly (P > 0.05) in T2 than the control. Moreover, the serum albumin improved insignificantly (P > 0.05) in T1 and T2 than the control. Serum alkaline phosphatase was significantly (P < 0.05) increased in treated fish with N. sativa; while serum glucose decreased significantly (P < 0.05) as compared with control ones. The hepatosoatic index (HSI) insignificantly (P > 0.05) decreased in T1 and increased insignificantly (P > 0.05) in T2 compared to the control. Also, the dietary 1 and 2 % N. sativa did not affect spleenosomatic index (SSI). The fish group which reared under oxygen deficiency exhibited remarkable decreased activity and increased random movement elicited by hypoxia changes in direction of swimming, while the fish groups fed diets with N. sativa showed slightly abnormal behavior changes. The mortality rates under oxygen deficiency were 100, 40 and 20% for control, T1 and T2, respectively. Under oxygen deficiency stress, the Hb and glucose did not differ between T1 and T2, while PCV% was increased significantly (P > 0.05) in T2 than that of T1; the same occurred (P < 0.05) with serum total protein concentration, globulin, and alkaline phosphatase activity, but serum albumin in T1 was higher than that of T2 (P < 0.05). There were no significant (P > 0.05) in HIS, SSI and GSI between treated groups with N. sativa and control ones. To conclude, the dietary supplementation with N. sativa at 1% and 2% displayed slight beneficial effects on growth performance and major effects on some blood constituents of O. niloticus.