Chinese Americans comprise the largest Asian subgroup in the U.S. Yet, little research has focused on the well-being of this population. This study aimed to (1) examine psycho-physiological health (psychological stress and fatigue) and lifestyle behaviors (sleep and physical activity) between Chinese Americans and whites, and (2) investigate whether race and lifestyle behaviors were independent predictors of psycho-physiological health. This study included 87 middle-aged healthy adults (41 Chinese Americans, 46 whites). Each participant underwent a two-night actigraphy-based sleep assessment. Chinese Americans reported higher psychological stress and fatigue, had poorer objective sleep outcomes (shorter sleep duration, lower sleep efficiency, and longer sleep onset), and engaged in lower physical activity levels than whites. Race and poor perceived sleep quality were independently associated with high psychological stress and fatigue. The findings warrant further exploration of social and cultural determinants of health in this minority group to reduce health disparities.