Objective: The objective of the present study was to study the degradation of third generation cephalosporin antibiotics viz. cefotaxime and cefoperazone using four yeast isolates under optimal conditions. Methods: The steps include screening of yeasts for degradation of cefotaxime and cefoperazone in minimal broth (MB). The effect of various parameters like pH, temperature, shaking speed, inoculum size and initial substrate concentration during degradation was studied. The effect of carbon and nitrogen as additional sources in MB on the yeast biomass production was tested. The degradation efficiency of four yeasts on cefotaxime and cefoperazone were calculated. Results: Under optimized conditions viz. pH 6.0, temperature 30°C, shaking speed of 120 rpm, inoculum dosage of 4{\%} (v/v) and initial cefotaxime concentration of 200 mg/L and cefoperazone concentration of 150 mg/L, maximum yeast growth was noted. No improvement in yeast growth was observed due to the addition of extra carbon and nitrogen sources. Among four yeast isolates, maximum degradation of 61{\%} cefotaxime at a concentration of 200 mg/L and 64{\%} cefoperazone at a concentration of 150 mg/L was shownby Candida sp. SMN04 under optimal condition. Conclusion: Therefore, based on the results of the present study, it can be concluded that the yeasts isolates can serve as degraders of cephalosporin antibiotics viz. cefotaxime and cefoperazone in aqueous environment.