Background: There are increasing reports of food safety issues associated with intensive production of fish which increase the chances of disease outbreaks from stressful growth conditions accompanying mass production and presence of bacterial pathogens. Methodology: Two hundred gastrointestinal tract (GIT) samples from two hundred African Cat Fish (Clarias glariepinus) were assessed for the presence of enteric Escherichia coli species including E. coli 0157, Enteropathogenic E. coli (EPEC) and Enteroinvasive E. coli (EIEC) which are traditionally associated with infantile gastroenteritis. The antibiotic resistance profile and Multiple Antibiotic Resistance Index (MARI) for these isolates were determined. The serogrouping of the E. coli isolates was done using E. coli agglutinating sera (Oxoid) and E. coli 0157 latex reagent (Oxoid). Antibiotic susceptibility was determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: A total of 35 (17.5%) E. coli isolates were recovered from the fish intestines among which 9 (25.7%) were EPEC and 2 (5.7%) were EIEC. No E. coli 0157 strain was recovered. Thirty-three (94.0%) isolates had a MARI greater than 0.2. Antibiotic resistance to cefoxitin and amoxicillinclavulanic acid were 77.1% and 74.3% respectively. All isolates were susceptible to meropenem and amikacin but all EPEC and EIEC isolates were AmpC (resistance to all penicillins, cephalosporins and beta lactamase inhibitors) positive. Conclusion: The isolation of EPEC and EIEC which can cause fatal gastroenteritis coupled with high MARI among isolates in this study represents a public health concern. Strict monitoring of administration of antibiotics in aquaculture is recommended.