The present study was performed to determine the efficacy of lipopolysaccharide (LPS) and levamisole on immune response and disease resistance in striped catfish and to compare their respective efficiency with the one of an antibiotic treatment after infection of fish by the bacteria Edwardsiella ictaluri. Fish were divided into 3 groups and each group was injected with LPS (3 mg/kg fish), levamisole (5 mg/kg fish) or phosphate buffer saline as control. At day 21st post immunostimulant injection, fish were bled for assaying immunological variables and then challenged with E. ictaluri. Three days after bacterial infection, an antibiotic treatment was applied into fish subgroups and mortality was compared daily between antibiotic treated and untreated fish until 2 weeks post-challenge. LPS and levamisole significantly enhanced non-specific immune responses such as respiratory burst, lysozyme and complement activity in fish compared with control (p < 0.05). Respiratory burst and complement activity significantly increased in levamisole groups when compared with LPS groups while lysozyme activity did not differ significantly between immunostimulant treatments. Total immunoglobulins significantly increased in levamisole treatment compared with control. After challenge test, accumulated mortality was reduced significantly in both non-antibiotic and antibiotic subgroups of LPS and levamisole compared with control. Moreover, no differences of mortality were observed between fish treated with levamisole or LPS without antibiotics and control fish treated with antibiotics. These results support the possible replacement of antibiotics in striped catfish farming by immunostimulants such as levamisole and LPS.