As in various freshwater and coastal marine ecosystems worldwide, seasonal bottom water hypoxia is a recurring phenomenon in Lake Erie’s central basin. While bottom hypoxia can strongly affect sessile benthic animals, its effects on mobile organisms such as fish are less understood. We evaluated the potential for bottom hypoxia to affect the growth rates of yellow perch Perca flavescens, a species of ecological and economic importance in the lake. To this end, we (1) conducted laboratory experiments to quantify the effects of reduced dissolved oxygen on consumption, somatic growth, and RNA:DNA ratios (an index of short-term growth) of young yellow perch and (2) explored the effects of bottom hypoxia on young yellow perch growth in Lake Erie’s central basin by collecting individuals in hypoxic and normoxic regions of the lake and quantifying their RNA:DNA ratios. Yellow perch consumption and growth in our experiments declined under hypoxic conditions (≤2 mg O2/L). While yellow perch RNA:DNA ratios responded strongly to experimental temperature, nucleic acid ratios were not significantly affected by dissolved oxygen or feeding ration. We did, however, observe a positive correlation between yellow perch growth and RNA:DNA ratios at low temperatures (11◦C). The nucleic acid ratios of yellow perch collected in Lake Erie varied spatiotemporally, but their patterns were not consistent with hypoxia. In short, while yellow perch consumption and growth rates respond directly and negatively to low oxygen conditions, these responses are not necessarily reflected in RNA:DNA ratios. Moreover, in central Lake Erie, where yellow perch can behaviorally avoid hypoxic areas, the RNA:DNA ratios of yellow perch do not respond strongly to bottom hypoxia. Thus, this study suggests that there is no strong negative effect of bottom hypoxia on the growth of young yellow perch in Lake Erie.