Abstract Background Recognition of loneliness as a health concern among adults stresses the need to understand the factors associated with loneliness. Research into factors of influence in the various phases of the adult life span (19–65 years) is scarce. Therefore, the associations between demographic, social and health-related factors and loneliness among young (19–34 years), early middle-aged (35–49 years) and late middle-aged adults (50–65 years) were explored. Methods A secondary analysis with a large cross-sectional dataset was performed. Data was collected from September to December 2016 in the Netherlands, by a self-report survey. Loneliness was measured using the De Jong-Gierveld Loneliness Scale. In total, 26,342 adults (19–65 years) participated (response rate: 34%). Multiple logistic regression analyses were performed to examine associations between demographic, social and health-related factors as independent variables, and loneliness as dependent variable among the three age groups. Results Prevalence of loneliness among young, early and late middle-aged adults was 39.7, 43.3 and 48.2%, respectively. Living alone, frequency of neighbour contact, perceived social exclusion, psychological distress, psychological and emotional wellbeing were consistently associated with loneliness across the groups. The association between ethnicity and loneliness was stronger among young and early middle-aged adults, compared to late middle-aged adults. Young adults showed the strongest association between contact frequency with friends and loneliness. The strength of association between financial imbalance and loneliness gradually decreased from young to late middle-aged adults. Educational level was associated with loneliness among young adults only, while an association between employment status and loneliness was found solely among early middle-aged adults. For late middle-aged adults only, perceived health was associated with loneliness. Frequency of family contact was associated with loneliness, only among ...