Abstract-This pilot study assessed the effects of cardiopulmonary exercise testing and cardiorespiratory fitness on plasma neuropeptide Y (NPY), allopregnanolone and pregnanolone (ALLO), cortisol, and dehydroepiandrosterone (DHEA), and their association with pain sensitivity. Medication-free traumaexposed participants were either healthy (n = 7) or experiencing comorbid chronic pain/posttraumatic stress disorder (PTSD) (n = 5). Peak oxygen consumption (VO 2 ) during exercise testing was used to characterize cardiorespiratory fitness. Peak VO 2 correlated with baseline and peak NPY levels (r = 0.66, p < 0.05 and r = 0.69, p < 0.05, respectively), as well as exercise-induced changes in ALLO (r = 0.89, p < 0.001) and peak ALLO levels (r = 0.71, p < 0.01). NPY levels at the peak of exercise correlated with pain threshold 30 min after exercise (r = 0.65, p < 0.05), while exercise-induced increases in ALLO correlated with pain tolerance 30 min after exercise (r = 0.64, p < 0.05). In contrast, exercise-induced changes in cortisol and DHEA levels were inversely correlated with pain tolerance after exercise (r = -0.69, p < 0.05 and r = -0.58, p < 0.05, respectively). These data suggest that cardiorespiratory fitness is associated with higher plasma NPY levels and increased ALLO responses to exercise, which in turn relate to pain sensitivity. Future work will examine whether progressive exercise training increases cardiorespiratory fitness in association with increases in NPY and ALLO and reductions in pain sensitivity in chronic pain patients with PTSD.Abbreviations: ALLO = allopregnanolone and pregnanolone, ANOVA = analysis of variance, BMI = body mass index, CPT = cold pressor test, CPX = cardiopulmonary exercise testing, CSF = cerebrospinal fluid, CSU = clinical studies unit, CV = coefficient of variation, DHEA = dehydroepiandrosterone, DHEA(S) = DHEA-sulfate, DSM-IV = Diagnostic and Statistical Manual of Mental Disorders-4th Edition, EKG = electrocardiogram, GABA = gamma-aminobutyric acid, GC-MS = gas chromatography-mass spectrometry, IV = intravenous line, NPY = neuropeptide Y, OEF = Operation Enduring Freedom, OIF = Operation Iraqi Freedom, PTSD = posttraumatic stress disorder, RIA = radioimmunoassay, TC = trauma-exposed healthy control, VA = Department of Veterans Affairs, VO 2 = oxygen consumption.