Considering the high and increasing prevalence of stress, approaches to mitigate stress-related biological processes become a matter of public health. Since supportive social interactions contribute substantially to mental and physical health, we set out to develop a social support stress management intervention and examined its effects on psychophysiological stress responses as well as self-reported stress in healthy women. In a parallel-group randomized controlled trial, registered in the DSRK (DRKS00017427), 53 healthy women were randomly assigned to a social support stress management or a waitlist control condition. All participants underwent a standardized psychosocial stress test where physiological and emotional stress responses were assessed by repeated measurements of cortisol, heart rate, heart rate variability and state anxiety. Also, all participants completed self-report questionnaires of perceived stress and social support at pre-intervention, post-intervention and follow-up four weeks later. Participants in the social support stress management showed a significantly attenuated integrated state anxiety response in comparison to those in the control condition, but conditions did not differ in any of the assessed physiological stress responses. The intervention significantly reduced perceived stress in comparison to the control condition, but perceived stress levels returned to baseline at follow-up. Our results indicated that the intervention had no effect on physiological responses to acute psychosocial stress, even though anxiety responses to stress were attenuated. However, the social support stress management intervention had a significant, albeit transient impact on perceived stress.