Health literacy (HL) is associated with preventive health behaviors. Self-efficacy is a predictor of health behavior, including physical activity (PA); however, causal pathways between HL and self-efficacy for PA are unknown, especially among Latinas who are at risk for chronic disease. To explore this potential relationship, secondary analyses were conducted on data [Shortened Test of Functional Health Literacy in Adults (STOFHLA), PA self-efficacy, and socio-demographics] from a 6-month, randomized controlled trial of a print-based PA intervention (n = 89 Spanish-speaking Latinas). Linear regression models revealed associations between HL and baseline self-efficacy in addition to changes in self-efficacy at 6-months. After controlling for significant covariates, higher HL scores were associated with lower baseline PA self-efficacy. Regardless of treatment assignment, higher HL scores at baseline predicted greater changes in PA self-efficacy at 6-months. HL may contribute to Latinas' improved PA self-efficacy, though further research is warranted. © 2012 Springer Science+Business Media, LLC.