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Aim:The trials were designed on 30 lambs of age below 2 weeks exhibiting the symptoms of colibacillosis.Materials and Methods: Isolation of organism and identification of pathogenic Escherichia coli was confirmed by standardcultural, microbiological, serological, and biochemical tests. Venous blood was collected aseptically for hematologicalstudies.Result: Bacteriological examinations of fecal sample were positive for E.coli and isolates identified on the basis ofmorphological, cultural, and biochemical characteristics provided further confirmation. Hematological indices recordedsignificant (p > 0.05) increase in the packed cell volume, total leucocyte count, lymphocyte, and neutrophil percentage,whereas biochemical indices recorded significant decrease in the serum glucose, protein and serum albumin/ globulin levels.Treatment regimen in four different groups, suggested, gentamicin and ciprofloxacin effective drugs followed by neomycinand co-trimoxazole.Conclusion: Study suggested significant (P > 0.05) alteration in hemato-biochemical parameters whereas results indicatedgentamicin and ciprofloxacin as most effective drugs.