- The Dead Sea region, the lowest in the world at 410 meters below sea level, is considered a potent climatotherapy center for the treatment of different chronic diseases. To assess the prevalence of chronic diseases and the quality of life of residents of the Dead Sea region compared with residents of the Ramat Negev region, which has a similar climate, but is situated 600 meters above sea level. An observational study based on a self-administered questionnaire. Data were collected from kibbutz (communal settlement) members in both regions. Residents of the Dead Sea were the study group and of Ramat Negev were the control group. We compared demographic characteristics, the prevalence of different chronic diseases and health-related quality of life (HRQOL) using the SF-36 questionnaire. There was a higher prevalence of skin nevi and non-inflammatory rheumatic diseases (NIRD) among Dead Sea residents, but they had significantly higher HRQOL mean scores in general health (68.7 ± 21 vs. 64.4 ± 22, p = 0.023) and vitality (64.7 ± 17.9 vs. 59.6 ± 17.3, p = 0.001), as well as significantly higher summary scores: physical component score (80.7 ± 18.2 vs. 78 ± 18.6, p = 0.042), and mental component score (79 ± 16.4 vs. 77.2 ± 15, p = 0.02). These results did not change after adjusting for social-demographic characteristics, health-related habits, and chronic diseases. No significant difference between the groups was found in the prevalence of most chronic diseases, except for higher rates of skin nevi and NIRD among Dead Sea residents. HRQOL was significantly higher among Dead Sea residents, both healthy or with chronic disease.