Background/Objectives: In recent years, increasing attention has been directed toward the human immune system and strategies to enhance its function. Whole-body cryother-apy (WBC), a short-term therapeutic application of extreme cold of about minus 90 de-grees, seems to show a positive influence on the immune system, physical pain, body composition and other human regulatory systems. Methods: In this one- armed prospec-tive monocentric observational study 20 adult participants underwent 18 sessions of cry-otherapy over 9 weeks (–90°C, 3 – 6 minutes each), followed by a 9-week post-intervention phase. Results: In many parameters of bioimpedance analysis, blood parameters and subjective perception of stress, statistically significant improvement could be found, especially directly after intervention phase. Some improvements persist till end of study time frame. Conclusions: The results of this pilot study underscore the impact of cryotherapy on pathways related to immune function and metabolic regulation. The results will pave the way for further randomized controlled trials that study and confirm the efficacy of WBC.