Post-traumatic stress disorder (PTSD) is a prevalent and debilitating condition associated with psychological conditions and chronic diseases that may be underpinned by dysfunction in the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis and chronic systemic low-grade inflammation. The objective of this pilot study was to determine psychological, ANS [heart rate variability (HRV)], HPA (salivary cortisol) and inflammatory (salivary C-Reactive Protein) responses to a bout of vigorous exercise in male first responders, military veterans and active duty personnel with (n = 4) and without (n = 4) PTSD. Participants (50.1 ±14.8 years) performed a thirteen-minute, vigorous intensity (70%-80% of heart rate max), one-on-one boxing session with a certified coach. Physiological and psychological parameters were measured before, during, immediately after to 30 min post-exercise, and then at 24 h and 48 h post. The effect sizes demonstrated large to very large reductions in HRV that lasted up to 48 h post-exercise in the PTSD group compared with unclear effects in the trauma-exposed control (TEC) group. There were unclear effects for depression, anxiety and stress as well as salivary biomarkers for both groups at all time-points. Findings may reflect stress-induced changes to the ANS for PTSD sufferers.