Although many musicians perceive music performance anxiety (MPA) as a significant problem, studies about the psychobiological and performance-related concomitants of MPA are limited. Using the biopsychosocial model of challenge and threat as theoretical framework, we aim to investigate whether musicians’ changes in their psychobiological responses and performance quality from a private to a public performance are moderated by their general MPA level. According to the challenge and threat framework, individuals are in a threat state when the perceived demands of a performance situation outweigh the perceived resources, whereas they are in a challenge state when the perceived resources outweigh the perceived demands. The resources-demands differential (resources minus demands) and the cardiovascular challenge-threat index (sum of cardiac output and reverse scored total peripheral resistance) are the main indices of these states. We postulate that the relationship between general MPA level and performance quality is mediated by these challenge and threat measures.