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Objectives Unmanned Combat aerial vehicles (UAVs) have evolved into assets of tactical-critical importance, thus safeguarding the occupational health of their operators is imperative. As UAV units of the Chinese are predominantly stationed in high-altitude regions, this study aimed to systematically assess the occupational health status and risk factors faced by these operators during their service, and to propose targeted protective measures. Methods A cohort of 62 active-duty UAV operators stationed in high-altitude regions was recruited to complete a self-administered questionnaire. The investigation was conducted utilizing a comprehensive framework encompassing occupational health assessment, risk factor evaluation, and protective measures analysis. Statistical methodologies employed included descriptive statistical analysis, symptom co-occurrence network analysis, and clustering pattern analysis. Results UAV operators in high-altitude regions exhibited significantly higher prevalence of neurological (67.74%), musculoskeletal (64.52%), and psychological symptoms (46.77%) compared to their counterparts in plain areas, with additional manifestations of otorhinolaryngological (67.74%) and respiratory symptoms (64.52%). Symptom co-occurrence network analysis identified “musculoskeletal pain” and “memory impairment “as central hubs. Clustering analysis revealed distinct risk stratification, with high-, medium-, and low-risk subgroups constituting 20.97, 40.32, and 38.71% of the cohort, respectively. Among risk factors, “unreasonable work schedules” and “high-altitude hypoxia” received the two highest risk scores. Regarding protective measures, “health education,” (0.66) “scientific training protocols,” (0.62) and “rational shift scheduling” (0.60) demonstrated the highest comprehensive effectiveness scores. Conclusion The UAV operator cohort in high-altitude regions demonstrated a notably poor occupational health status. “musculoskeletal pain” and “memory impairment “were identified as critical intervention targets. Given the prominent roles of “high-altitude hypoxia” and “unreasonable work-rest schedules” as dominant risk factors, occupational health strategies should be strategically redirected from over-reliance on personal protective equipment toward prioritized investment in efficient management systems. These include implementing “scientific training protocols,” enhancing “health education,” and establishing structured “work-rest rotation systems.” Simultaneously, essential oxygen supply and noise reduction equipment should be deployed at high-altitude workplaces.