Angiotensin-II receptor blockade (ARB) has been associated with reduced posttraumatic stress disorder (PTSD) symptoms in population-based studies. Pre-clinical evidence further suggests that ARB may play a critical role in modulating the physiological stress response, with results showing reduced cortisol secretion in rodents after chronic ARB, and reduced sympathetic activity in humans watching traumatic films after single-dose ARB. However, despite the critical role of cortisol in PTSD development, ARB effects on the human cortisol response have not been probed directly. In this double-blind study, 60 healthy participants were randomised to receiving a single-dose of the angiotensin-II receptor blocker losartan (50 mg) or placebo, prior to undergoing a computerised 20-minute psychosocial stress paradigm lasting 20 min. Salivary cortisol was assessed pre-stress and directly after the stress paradigm, as well as 20 min post-stress and 40 min post-stress. In addition, subjective stress, heart rate and heart rate variability were measured. After losartan and placebo, increases in salivary cortisol, subjective stress, heart rate, and heart rate variability in response to the stress task were seen, but these did not differ between groups. Exploratory analyses showed that while hormonal contraception users showed a blunted cortisol response to stress, losartan administration seemed to restore their cortisol response while not affecting non-users. This study indicates that single-dose ARB may not affect the stress response towards a psychosocial stressor of moderate intensity in healthy humans, encouraging future research to explore the effects of longer-term ARB.