This work was carried out to investigate Pseudomonal septicemia in Nile tilapia, Oreochromis niloticus, at Assiut governorate and to evaluate the effects of oral administration of black cumin Nigella sativa on resistance against Pseudomonas aeraginosa infection. A total of 100 Nile tilapia were collected from River Nile and El-Ibrahemia canal, Assiut governorate, and were subjected to clinical and bacteriological examination. Pseudomonase like isolates were detected from 29 out of 100 collected and examined fish samples (The incidence of pseudomonase infection was 29%). Biochemically, the collected isolates were identified as P. aureginosa and P. putida and other unidentified pseudomonase species. The organisms were mainly isolated from liver, spleen and kidney. The pathogenicity of the isolated P. aureginosa from Nile tilapia was confirmed by an experimental pathogenicity challenge. A total of 90 Nile tilapia were divided into two equal groups with three replicates to investigate the effect of dietary supplementation of black cumin on diseased resistance throughout the experimental challenge. Fish of the first group were fed on basic diet, while fish of the second group fed on basic diet with 3% black cumin /kg diet (3 g. black cumin /100 g diet) for 30 successive days. Experimental challenge was done by immersion wherethe infected fish showed typical signs of pseudomonal septicemia; redness all over the body, ulceration, scales detachment, darkening of body and congestion of all internal organs. Cumulative mortalities of fish challenged were significantly less in groups fed on black cumin diet (13.33%) than those fed on the basic diets (53.33%). Moreover, lesions and symptoms were less or sporadically seen in group treated with black cumin. These results showed black cumin improve the fish resistance to disease.