Active duty (AD) women suffer with chronic pelvic pain (CPP) while providers tackle diagnoses and treatments to keep them functional without contributing to the opioid epidemic. The purpose of this randomized trial was to determine the effectiveness of noninvasive, self-explanatory mindfulness-based stress reduction (MBSR) or self-paced healthy lifestyle (HL) interventions on CPP in AD women. A 6-week, interventional prospective study with AD women aged 21-55 years at Mountain Home (MTHM), Idaho, was conducted. Women were randomly assigned to MBSR ( = 21) or HL ( = 20) interventions. The primary outcome was pain perception. The secondary outcomes were depression and circulating cytokine levels. Women in the MBSR group exhibited reduced pain interference ( < 0.01) and depression ( < 0.05) alongside decreased interleukin (IL)-4 ( < 0.05), IL-6 ( < 0.05), eotaxin ( < 0.05), monocyte chemoattractant protein-1 ( = 0.06), and interleukin-1 receptor antagonist (IL-1ra) ( < 0.01) and increased vascular endothelial growth factor ( < 0.05). Women in the HL group did not have changes in pain; however, they did exhibit reduced depression ( < 0.05) alongside decreased granulocyte-macrophage colony-stimulating factor ( < 0.05) and increased tumor necrosis factor alpha ( < 0.05), stromal cell-derived factor-1 ( < 0.01), and IL-1ra ( < 0.01). AD women receiving MBSR or HL had reduced depression scores and altered circulating cytokine levels; however, only those receiving MBSR had reduced pain perception. Findings support MBSR as an effective and viable behavioral treatment for AD women suffering from CPP and provide premise for larger randomized controlled studies. MOCHI-An RCT of mindfulness as a treatment for CPP in AD Women NCT04104542 (September 26, 2019).