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This paper examines potential associations of loneliness with laboratory data and specific psychosocial and behavioral attitudes. The sample collection took place in an urban Primary Health Care unit between May and July 2023, consecutively, and once exclusion criteria were implemented. Participants were aged between 40 and 75 years. Routine laboratory test results upon study initiation and six months before were used. The University of California, Los Angeles (UCLA), Loneliness Scale (Version 3), blood glucose, serum lipids, Fibrosis-4 index, and Creatinine Clearance (CrCl) were assessed through hierarchical multiple logistic regression analysis. Based on full model (3rd) analysis, those who were engaged in an individual sport or activity or had contacts with more friends presented significantly lower odds for increased loneliness levels (odds ratio (OR): 0.28 [95% confidence interval (CI) 0.09–0.91], p = 0.034 and OR: 0.76 [95%CI 0.66–0.88], p < 0.001, respectively). The consumption of alcohol was associated with increased loneliness (OR: 5.55 [95%CI 1.42–21.63], p = 0.014). Elevated triglyceride levels were linked with moderate or no loneliness (OR: 0.20 [95%CI 0.05–0.83], p = 0.026), while an increased LDL/HDL atherosclerotic index was related to increased subjective loneliness (OR: 4.50 [95%CI 1.12–18.13], p = 0.035). The need for holistic approaches—involving primary care personnel—in understanding and addressing loneliness, recognizing its multifaceted nature as well as the diverse factors that contribute to this issue, is considered challenging. [ABSTRACT FROM AUTHOR]