Background. The goal of this pilot study was to determine the magnitude and direction of intervention effect sizes for inflammatory-related serum markers and relevant health outcomes among breast cancer survivors (BCSs) receiving a physical activity behavior change intervention compared with usual care. Methods. This randomized controlled trial enrolled 28 stage I, II, or IIIA BCSs who were post-primary treatment and not regular exercisers. Participants were assigned to either a 3-month physical activity behavior change intervention group (ING) or usual care group (UCG). Intervention included supervised aerobic (150 weekly minutes, moderate-intensity) and resistance (2 sessions per week) exercise that gradually shifted to home-based exercise. Outcomes were assessed at baseline and 3 months. Results. Cardiorespiratory fitness significantly improved in the ING versus the UCG (between-group difference = 3.8 mL/kg/min; d = 1.1; P =.015). Self-reported sleep latency was significantly reduced in the ING versus the UCG (between group difference = -0.5; d = -1.2; P =.02) as was serum leptin (between-group difference = -9.0 ng/mL; d = -1.0; P =.031). Small to medium nonsignificant negative effect sizes were noted for interleukin (IL)-10 and tumor necrosis factor (TNF)-α and ratios of IL-6 to IL-10, IL-8 to IL-10, and TNF-α to IL-10, whereas nonsignificant positive effect sizes were noted for IL-6 and high-molecular-weight adiponectin. Conclusions. Physical activity behavior change interventions in BCSs can achieve large effect size changes for several health outcomes. Although effect sizes for inflammatory markers were often small and not significant, changes were in the hypothesized direction for all except IL-6 and IL-10. © The Author(s) 2012.