Inbreeding has profound implications in fields ranging from evolutionary biology to medicine. Most cultured aquatic species are only partially domesticated and highly fecund and are, therefore, expected to have higher genetic load and more severe inbreeding depression than species with lower fecundity and/or longer histories of domestication. Marine bivalves such as oysters are extreme in this regard, and previous studies have demonstrated that self-fertilization, brother/sister matings, and cousin/cousin matings in Pacific oysters (Crassostrea gigas) reduce growth and survival. It is unclear, however, whether these effects can be extrapolated to lower levels of consanguinity such as those expected in natural populations or the founders used to initiate cultured strains or selective breeding efforts. To address this without the need for extensive pedigree information, we studied inbreeding in a naturalized population of Pacific oysters using molecular marker-based estimates of parental relatedness calculated from multilocus microsatellite genotypes. We produced 34 full-sib families using randomly mated parents collected from a naturalized population in Dabob Bay (Washington, USA) and planted them in intertidal and subtidal conditions in Dabob Bay and Yaquina Bay (Oregon, USA). Using 16 microsatellite loci, we estimated the degree of inbreeding of each pair's progeny in three ways: (1) identity ( I ) or the expected homozygosity of the progeny based on their parents' genotypes estimated using the IDENTIX program, (2) a moment-based estimator of the pair-wise coefficient of relatedness ( W ) of each parental pair estimated using the MER program of Wang, and (3) a modified estimator of the pair-wise coefficient of relatedness ( K ) designed specifically to accommodate null alleles, which were common in the Dabob Bay population and estimated using the ML-RELATE by Kalinowski. Using a composite analysis of variance approach to partition the total among-family variation into components attributable to inbreeding and all other family-level effects, we found statistically significant negative relationships between all three estimators of inbreeding and the survival of their progeny when we analyzed all location/exposure combinations simultaneously and in 7 of the 12 separate tests examining each location/exposure combination separately. However, for 4 of the 5 nonsignificant tests, P < 0.07 using K estimator of relatedness, which makes the potentially unreasonable assumption that all parents have inbreeding coefficients (F) of zero. Further, these relationships were strongest at the site with the highest mortality, indicating that inbreeding depression may be more severe in a more stressful environment. Finally, we briefly outline potential strategies for using molecular marker-based estimates of relatedness to improve the genetic composition of new founder populations, incorporation of relatedness information in selective breeding efforts, and minimizing inbreeding effects in established cultured oyster populations.