In insects changes in lipid metabolism may underlie a trade-off between cold resistance and starvation resistance. To test this we examined correlated responses in independent sets of Drosophila melanogaster lines selected for increased cold resistance and increased starvation resistance. The starvation lines showed correlated patterns found in other D. melanogaster populations selected for this trait, including higher lipid levels and increased resistance to desiccation, although the selected lines did not show a longer development time as found in some other studies. Consistent with the trade-off hypothesis, selected lines with increased starvation resistance showed decreased resistance to a cold stress as measured by mortality, whereas selected lines with increased cold resistance showed a decrease in starvation resistance. To counter the possibility of inadvertent selection accounting for these patterns, selected and control lines from both selection regimes were crossed to form mass bred populations, which were left for four generations prior to establishing isofemale lines. By scoring starvation and cold resistance in these lines derived from both sets of selection regimes, we confirmed the negative association between resistance to these stresses in females but not in males. Potential implications of this trade-off for surviving cold conditions when food resources are limiting are discussed.