<p>Human presence and work in Antarctica occur under challenging climatic, psychophysiological, and social conditions. The health of expedition participants is a critical factor, and a pre-expedition medical assessment is extremely important. We evaluated the prognostic significance of previously identified immune accentuations on the health of Ukrainian Antarctic Expedition overwintering participants. Immunophenotyping was performed on 43 male winterers before the expedition. Their health and laboratory parameters of the immune system were tracked the entire expedition. According to the results, winterers with favorable and unfavorable kinds of adaptation showed differences in immunophenotypic indicators. The majority of winterers with favorable adaptation had T-helper (CD3+CD4+) levels (&gt; 35%), balanced (&lt; 24%) expression of HLA-DR on cytotoxic T-lymphocytes (CD3+CD8+), proportions and absolute levels of NK lymphocytes (5–18% and 100–400). In contrast, winterers with unfavorable adaptation exhibited balanced levels significantly less frequently. NK cell levels in the range of 5–18% were virtually absent in winterers with unfavorable adaptation. The combination of two diagnostically significant immune parameters yields higher accuracy. Increased expression of HLA-DR on cytotoxic T-lymphocytes and elevated NK-lymphocyte content significantly enhance the prognostic value of the diagnostic algorithm. In all winterers, cortisol levels significantly increased in the first quarter of the expedition compared to baseline, followed by fluctuations. Cortisol levels returned to baseline after the expedition. The results demonstrate that staying in Antarctica requires adaptive processes that are directly dependent on the balanced functioning of the immune system. Stressful environment condition, in conjunction with immune accentuations, complicates successful adaptation.</p>