Whole-Body Cryotherapy at −90 °C for 9 Weeks: Effects on Immune Function, Stress, and Immune-Related and Vascular Blood Parameters in Healthy Adults—Results of an Exploratory One-Armed Pilot Study

<b>Background/Objectives</b>: Whole-body cryotherapy (WBC), a brief exposure to extreme cold (-90 °C), has been proposed to modulate immune, metabolic, and stress-related pathways. This exploratory one-armed pilot study investigated the effects of an 18-session WBC protocol on immune markers, body composition, and perceived stress in healthy adults. <b>Methods</b>: Nineteen participants (mean age 52.9 ± 9.8 years) completed 18 WBC sessions over 9 weeks (3-6 min each), followed by a 9-week follow-up. Assessments were performed at baseline (M1), post-intervention (M2), and follow-up (M3). Primary outcomes included immune parameters (lymphocytes, granulocytes, cytokines, soluble ACE2), body composition (waist circumference, water compartments, lean mass), and perceived stress (Trier Inventory for Chronic Stress, TICS). <b>Results</b>: Waist circumference decreased from 83.8 ± 5.7 cm (M1) to 80.2 ± 4.2 cm (M2) (<i>p</i> = 0.001; M1 vs. M2; <i>p</i> = 0.004). Total body water (<i>p</i> = 0.008), lean body mass (<i>p</i> = 0.008), intracellular water (<i>p</i> = 0.005), and extracellular water (<i>p</i> = 0.021) also showed time-dependent effects. Immune modulation included increased lymphocytes (25.6 ± 7.1% to 29.3 ± 8.3%, <i>p</i> = 0.012) and decreased granulocytes (63.5 ± 6.8% to 58.7 ± 7.9%, <i>p</i> = 0.011) at M2. Anti-inflammatory IL-10 (virus-stimulated) rose markedly (33.5 ± 29.3 to 63.5 ± 50.5 pg/mL, <i>p</i> < 0.001), while IFN-γ (virus-stimulated) increased over time (<i>p</i> = 0.031). Soluble ACE2 decreased at follow-up (0.5 ± 0.7 to 0.3 ± 0.4 ng/mL, <i>p</i> = 0.029). Perceived stress improved in several TICS domains, including Work Overload (<i>p</i> = 0.009) and Pressure to Succeed (<i>p</i> = 0.018). <b>Conclusions</b>: This pilot study demonstrates that repeated WBC at -90 °C induces measurable changes in immune regulation, body composition, and perceived stress. These findings support the feasibility and potential physiological relevance of WBC and providing effect-size estimates for future randomized controlled trials.