The physiological characteristics of working with protective clothing in severely cold stores (below −20 °C), as a typical artificial cold environment, are reviewed mainly from our field and experimental studies. Most cold stores in Japan are operated between −20 °C and −30 °C. The most frequent physical complaint among cold-store workers was “lumbago” followed by “It’s easy to catch a cold,” “neuralgia,” and “rheumatism.” Workers in severely cold stores are at a greater risk of health problems, especially musculoskeletal disorders. When the work load increases in severely cold environments, the decrease in the core temperature is suppressed, and workers feel less cold. However, the finger skin temperature does not change due to the increased in workload, causing a greater decrease in manual performance. Although the duration of cold exposure per stay in a cold store was very short, forklift workers entered cold stores frequently. Cold stress and decrease in workers’ performance were the same as those for continuous exposure to cold. Cold stores hold large volumes of frozen fish/meat, and workers must perform night work to deliver them to markets that open in the early morning. Since the peripheral skin temperature of workers at night is higher than that in the afternoon, they were less likely to feel cold or pain sensations at night. However, there was a marked decrease in rectal temperature and manual performance. There is an increased risk of both hypothermia and accidents among those working at night. The burden of labor on women, middle-aged, and older people under severe cold conditions, the effects of cold adaptation, and the burden of labor under ultralow temperatures (below −40 °C) will be important subjects for future research.