Co-oxidation of trivalent chromium (Cr(III)) to hexavalent chromium (Cr(VI)) during ozonation of organic pollutants represents a common problem facing the implementation of in situ chemical oxidation (ISCO) for environmental remediation. A laboratory study was conducted by using groundwater and saturated soil samples from a field site in Sacramento, California, to determine optimal O3 dosage to achieve satisfactory remediation of MTBE while minimizing co-oxidation of Cr(III) to Cr(VI). Total oxidant demand was determined (28.33mg O3 L−1) and used as the benchmark to establish a range of ozone dosages for the study. Concentration changes in MTBE and chromium were monitored at O3 dosages less than and greater than the benchmark. The results indicate that MTBE is preferentially oxidized by ozone at and below the indicated benchmark dosage prior to the oxidation of Cr(III) to Cr(VI). The resultant O3 dosage of 28.33mgL−1 was applied in the field implementation, verifying that the O3 can be applied in a controlled manner to remediate MTBE while minimizing the formation of Cr(VI).