Loneliness is a significant public health problem due to the physical, cognitive and psychosocial changes that occur with ageing. Social support and empowerment can be particularly important for older people, alleviating loneliness and improving mental well-being. The present study aimed to investigate the mediating role of health empowerment in the relationship between perceived social support and loneliness among nursing home residents. The study was conducted with a correlational design and reported based on STROBE checklist. The study was completed with 277 older adults aged 65 years and over residing in nursing homes. Process Macro Model 4 was conducted to verify the mediating role. The response rate was 95.6%. Most older adults experienced a feeling of loneliness, and the level of social support and empowerment perceived by most of them was high. The study found a mediating role of health empowerment in the relationship between social support and loneliness. Social support was significantly positively correlated with health empowerment and negatively correlated with loneliness. The significant standardised indirect effect of health empowerment on loneliness evidenced a partial mediating role. This study concluded that health empowerment has a partial mediating role in the effect of perceived social support and loneliness. Nurses could develop effective strategies for preventing psychosocial problems in nursing home residents. Nurses could contribute significantly as educators, counsellors and leaders in planning interventions to empower older adults. By empowering older adults regarding healthcare, nurses could increase their perception of social support, improving mental health by increasing effective coping with loneliness. Nurses could design intervention programmes to increase perceived social support, as well as health empowerment levels, and reduce older adults' loneliness in nursing homes. Older adults completed the instruments.