We examined the effects of burnout and vigor on the incidence of hyperlipidemia. Based on the bivariate theoretical approach to negative and positive affects and on past studies on the prediction of blood lipids by burnout and vigor, we expected increases from Time 1 (T1) to Time 2 (T2) in burnout levels to be associated with an increase in the risk for hyperlipidemia and T1–T2 increases in vigor levels to be associated with a decrease in the risk of hyperlipidemia. Our sample consisted of 3,337 healthy employees (2,214 men and 1,123 women) who were followed up for about 27 months on average. Burnout and vigor were assessed by well-validated multiple-item instruments. We used logistic regressions and controlled for variables associated with blood lipids as well as with vigor and burnout. We cross-validated all self-reported hyperlipidemia by their T2 lipids levels. As expected, we found that T1–T2 increases in vigor levels were associated with a decreased risk of hyperlipidemia. However, the T1–T2 change in burnout levels was marginally significant (p = .06) in predicting hyperlipidemia. We consider our finding that vigor and burnout are independently associated with the risk of hyperlipidemia as providing support for the bivariate approach to affective states. In addition, our major finding suggests a possible mechanism via which vigor influences physical health outcomes.