Several protocols have been developed for inducing acute stress in laboratory settings. Still, effectively eliciting stress in a neuroimaging environment remains challenging. Here, we describe the evaluation of a combined physical and psychosocial stress protocol (n = 42). The imaging Maastricht Acute Stress Test (iMAST) consists of a 5-min preparation phase and a 10-min acute stress phase, with alternating trials of cold pressor stress generated through an advanced thermal stimulator and mental arithmetic challenges along with social-evaluative pressure (i.e., negative feedback). Results demonstrate that participants displayed meaningful subjective stress responses, as well as significant increases in salivary alpha-amylase and cortisol levels. Our data show that the iMAST may prove to be a potent alternative to existing imaging stress paradigms to explore poststress neuronal changes and brain determinants of resilience.