The objectives were to evaluate the effects of elevated pre- and postpartum nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) concentrations during the transition period on reproductive performance and milk production in dairy cattle. In a prospective cohort study of 91 freestall, total mixed ration-fed herds in the northeastern United States, blood samples were collected from approximately 15 prepartum and 15 different postpartum transition animals in each herd. All samples were stratified based on pre- or postpartum status at the time of sample collection, and 2,259 and 2,290 animals were used to evaluate reproductive and milk production performance, respectively. Reproductive performance was assessed by time to conception within 70 d post-voluntary waiting period (VWP) and milk production was assessed using mature-equivalent 305-d (ME305) milk yield estimated at 120 d in milk. While controlling for body condition score (BCS), calving season, median ME305 milk production, and parity, NEFA and BHBA concentrations were evaluated with time to event analysis to investigate reproductive performance. These same predictor variables were used to determine the effects of elevated NEFA and BHBA concentrations on ME305 milk yield with herd as a random effect. Heifers and cows were grouped in the final analyses if the results between groups were similar. In all animals sampled prepartum, the risk of pregnancy within 70 d post-VWP was reduced by 19% when NEFA concentrations were ≥0.27mEq/L. In all animals sampled postpartum, those with NEFA concentrations ≥0.72mEq/L had a 16% decrease in risk of pregnancy and those with BHBA concentrations ≥10mg/dL had a 13% decrease in risk. In cows and heifers, ME305 milk yield was decreased by 683kg when prepartum NEFA concentrations were ≥0.33mEq/L. In heifers sampled postpartum, ME305 milk yield was increased by 488kg when NEFA concentrations were ≥0.57mEq/L and increased by 403kg when BHBA concentrations were ≥9mg/dL. In cows sampled postpartum, ME305 milk yield was decreased by 647kg when NEFA concentrations were ≥0.72mEq/L and decreased by 393kg when BHBA concentrations were ≥10mg/dL. With the exception of milk production in heifers, this study indicates that increased concentrations of serum NEFA and BHBA had a detrimental effect on reproductive performance and milk production.