What is already known about this subject Physical activity declines as children enter puberty. Leptin is cross-sectionally associated with physical activity, but there are conflicting findings on the magnitude and direction of this association. Leptin concentrations fluctuate during puberty, and may impact energy balance. What this study adds Leptin predicts the decline in physical activity during the start of puberty independent of central adiposity. Based on a median split of leptin, girls with low leptin levels have higher levels of physical activity than girls with high leptin levels at the start of puberty. Leptin levels at the start of puberty may provide a biological basis for the age-related physical activity decline in girls. Background Leptin may influence moderate to vigorous physical activity (MVPA) at the start of puberty. The direction and magnitude of this association are unclear. Objectives To determine the effect of baseline leptin on MVPA over 1 year in minority girls at high risk for obesity. Methods Data came from TRANSITIONS, a longitudinal observational study on the age-related MVPA decline. Fifty peripubertal girls aged 811 years at baseline participated. Baseline leptin (ng?mL-1) was collected via a duplicated assay using a double antibody radio immune assay. MVPA (min?d-1) was measured using accelerometers for at least four 10-h days on a quarterly basis for up to 1 year. Results Continuous leptin was negatively related to MVPA (P?=?0.001) independent of central adiposity at baseline and predicted the MVPA decline over 1 year (P?=?0.002). For descriptive purposes, baseline leptin was dichotomized at the sample median into high leptin and low leptin categories to determine whether MVPA trajectories differed between these groups. Girls with low leptin at baseline had significantly higher levels of MPVA at baseline, visit 1 and visit 2 compared to girls with high leptin. Conclusions High leptin levels predicted nearly a 12.6% decline in MVPA over 1 year. These findings provide support for the biological basis of declining MVPA as girls enter puberty.