Previous research suggests obesity is negatively related to cognitive functioning and academic outcomes in addition to physical health. However, not much is known about this association in early childhood or potential physiological underpinnings. Biomarkers related to obesity have been associated with cognition, in particular the adipokine leptin, and pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). These associations may be further exacerbated for children who experience early life stress. With a sample of low-income preschoolers, the current study examined associations between obesity-related biomarkers and aspects of behavioral and cognitive school readiness. Partial correlations controlling for child age show hypothesized negative associations between pro-inflammatory cytokines and school readiness, while leptin was positively associated with cognitive school readiness and body mass index (BMI) z-score. Findings suggest connections between obesity, physiology, and school readiness need further examination, but may have implications for early childhood education and health interventions.