The prevalence of obesity among children in the United States has increased rapidly during the past few decades. Research into social and behavioral determinants of obesity could lead to innovative strategies for prevention. The objective of the present study was to examine the association between childhood obesity and preschool enrollment and number of hours in child care among low-income preschool-aged children who were participants in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC). We conducted a case-control study including 556 3- to 4-year-old children who were either obese (BMI > 95th percentile of reference standard) or normal-weight (BMI 25-75th percentile). The population was largely (96%) Hispanic, an ethnic group that has one of the highest rates of overweight and obesity in adults and children in the US. In multiple logistic regression analysis, controlling for a variety of psychosocial and cognitive home environment variables, key demographics and maternal variables, the odds ratio of being obese was 0.61 for children who attended preschool more than 4 days a week (95% CI: 0.41-0.90). Watching television or videos for an hour or more on a typical day (odds ratio 1.71 (95% CI 1.07-2.75)), and higher maternal BMI (odds ratio 1.08 (95% CI 1.05-1.11)) were independently related to odds of obesity. The impact of preschool attendance and TV viewing are potentially instructive in terms of preventive interventions for children at this age.