In animal populations, sib mating is often the primary source of inbreeding depression (ID). We used recently wild-caught Drosophila melanogaster to test whether such ID is amplified by environmental stress and, in males, by sexual selection. We also investigated whether increased ID because of stress (increased larval competition) persisted beyond the stressed stage and whether the effects of stress and sexual selection interacted. Sib mating resulted in substantial cumulative fitness losses (egg to adult reproduction) of 50% (benign) and 73% (stressed). Stress increased ID during the larval period (23% vs. 63%), but not during post-stress reproductive stages (36% vs. 31%), indicating larval stress may have purged some adult genetic load (although ID was uncorrelated across stages). Sexual selection exacerbated inbreeding depression, with inbred male offspring suffering a higher reproductive cost than females, independent of stress (57% vs. 14% benign, 49% vs. 11% stress).