Loneliness is increasingly recognized as a significant determinant of physical and mental health, particularly during the transition to older age. Understanding its determinants is essential for developing early prevention strategies. This study aimed to describe levels of loneliness in adults aged 55–75 years and examine associations with sociodemographic and clinical variables. A cross-sectional study was conducted with 150 participants residing in the municipalities of Évora and Vendas Novas, Portugal. Data were collected through a sociodemographic and clinical questionnaire and the UCLA Loneliness Scale. Descriptive and inferential analyses were performed. Overall, most participants reported low loneliness levels; however, a vulnerable subgroup emerged. Loneliness was reported by 38% of participants, while 13.3% experienced social isolation and 10% reported affinity-related difficulties. Higher loneliness scores were significantly associated with being female, having lower educational attainment, being on sick leave, living alone, and having a diagnosed chronic illness. These findings highlight that, despite generally low levels of loneliness, specific groups are at increased risk and require targeted interventions. The study underscores the importance of integrating loneliness screening into primary care and chronic disease management, as well as developing community-based strategies to promote social connection and healthy ageing.