Uric acid, an end product of the purinergic system, plays a role in several physiological systems that are responsive to stress. However, few studies have examined whether (1) uric acid concentrations change in response to acute stress, and (2) there are cross-system associations where uric acid might influence other physiological system responses to acute physical stress. The present study measured indices of the purinergic, hypothalamic-pituitary-adrenal axis, sympathetic, and parasympathetic systems (uric acid, cortisol, pre-ejection period, and root mean square of successive differences, respectively) in response to a standardized acute physical pain stressor, the cold pressor task. A diverse sample of participants (n = 67; mean age = 20.5 years, 52% female; 48% male) from a larger study completed anthropometric measurements and took part in a room temperature water task followed by the cold pressor task and sociodemographic questionnaires. Throughout the study, electrocardiography and impedance cardiography were measured continuously, and five saliva samples were collected that were later assayed for cortisol and uric acid. Descriptively, uric acid increased about 32 min following completion of the cold pressor. Resting uric acid concentrations were not associated with the autonomic nervous system response, but higher resting uric acid concentrations were associated with increased cortisol concentrations. Future research should examine the extent to which the purinergic system influences, and is influenced by, other types of stress and other physiological systems. The current findings highlight the potential role of an understudied biomarker and physiological system in the stress literature and have implications for basic and mechanistic researchers who study psychoneuroendocrinology, stress, and health.