The impact of motivational climate on physiological responses to psychological stress remains largely unknown. The purpose of this experimental investigation was to examine the psychological and physiological stress and motivational responses of college students (N = 57, Mage = 20.34) during a 30-minute instructional juggling session that was either caring, task-involving (C/TI) or ego-involving (EI). Cortisol and inflammation were assessed at six time points over the 2-hr study, and participants completed pre- and post-questionnaires. As hypothesised, the EI climate elicited concerning responses including greater psychosocial and state cognitive stress, negative affect, and cortisol, while the C/TI climate yielded adaptive responses including what may be a multifaceted physiologically protective mechanism to performance-related stress. Specifically, the C/TI climate yielded greater sTNFαRII, performance and social self-esteem, positive affect, and coping appraisals. Results suggest C/TI climates procure psychological and physiological responses that facilitate performance and well-being and foster a greater interest in physical activity.