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Escherichia colt and Staphylococcus aureus species though opportunist pathogens, are becoming a global clinical problem in both human and veterinary medicine. This study was designed to determine the antibiotic susceptibility patterns of beta-lactamase-producing E. coli serotypes and S. anions strains isolated from chickens in the Maiduguri Arid zone, Nigeria. Various tissue samples from apparently healthy and diseased chickens were collected and examined or the presence of E. coli and S. aureus. Isolates were identified by relevant biochemical tests. beta-lactamase-producing strains of the isolates were determined by the chromogenic cephalosporin method, using nitrocefin-impregnated sticks and cephalosporin (nitrocefin) solution. The antibiotics susceptibility patterns of the isolates were determined for ten antibiotics (ampicillin, chloramphenicol. cephalex in. ciprofloxacin, lincomycin, doxycycline, tetracycline, tylosin, tylosin tartrate and penicillin) by the micro-broth dilution method. E. coli was isolated in 805 and S. aureus in 660 of 1300 tissue samples examined; from which 89 (11.1%) and 58 (8.8%) were beta-lactamase-positive isolates respectively. Out of 540 E. roll isolates serotyped, 57 (10.6%) serogroups were identified from which 17 (29.8%) were serogroups O1, 5 (8.8%) were O2, and 2 (3.5%), 9(15.8%), 6(10.5%) and 18(31.6%) were serogroups O26, O78, O86 and O141 respectively, whilst, 483 (89.4%) isolates were not typable with the available sera. Serogroups O141, O1 and O78 were more frequently isolated and serogroups O1 and O78 were more prevalent in sick chickens than in healthy chickens. E. coli exhibited high resistance to ampicillin, chloramphenicol, tetracycline, lincomycin, penicillin and tylosin with MIC values >8.0 mu g/uL, as did S. aureus to all the antibiotics tested with MIC values >8.0 mu g/mu L. In conclusion, the study has demonstrated the presence of E. coli serotypes and S. aureus in various tissues of chickens and their antibiotic susceptibility patterns, clearly demonstrating multiple drug resistance.