Microorganisms can initiate the degradation of organic compounds by oxygenation reactions that require the investment of energy and electrons. This diversion of energy and electrons away from synthesis reactions leads to decreased overall cell yields. A thermodynamic method was developed that improves the accuracy of cell yield prediction for compounds degraded through pathways involving oxygenation reactions. This method predicts yields and stoichiometry for each step in the biodegradation pathway, thus enabling modeling a multi-step biodegradation process in which oxygenations occur and intermediates may persist. EDTA and benzene biodegradation are presented as examples. The method compares favorably with other yield prediction methods while providing additional information of yields for intermediates produced in the degradation pathway.