The purpose of this study was to examine the relation between measures of students’ physical well-being and self-perception and their academic achievement. Specifically, we look at students’ social support for physical activity, physical activity perceptions, self-concept, self-efficacy, health behaviors, and cardiorespiratory fitness (as measured by the progressive aerobic cardiovascular endurance run [PACER] test). Students (n = 697 fifth graders) were surveyed at the beginning of the school year. A two-group path analysis revealed notable relationships between the predictor variables and proximal and distal outcomes, with some paths moderated by sex. One relationship that was significant for both sexes was cardiorespiratory fitness, as it was the only significant predictor of achievement. This effect was moderate to large for the female students (R2Math=36%; R2Read=15%) and small to large for the male students (R2Math=26%; R2Math=10%). These findings can be used to guide future research and educational prevention and intervention efforts