We conducted the largest study to date to examine the true associations between loneliness and personality traits combining self and informant reports. Using a method described by Mõttus and colleagues (2023) we obtained noise- and bias-free ‘true’ correlations (rtrues), which were used to produce regression model estimates of the true independent associations (βtrues) of age, sex and Big Five personality domains with loneliness across three multicultural samples (Estonian-speaking, n = 20,893; Russian-speaking, n = 762; English-speaking, n = 600). Using this method, personality traits predicted 54–62% of variance in loneliness, compared to 26–33% when using methods limited to just self-report or informant-report data. Across samples, we found strong independent relationships between loneliness and Neuroticism (βtrues around 0.7) when controlling for other personality traits. Loneliness had robust, though comparatively weaker, associations with Extraversion (βtrues around 0.25) and Agreeableness (βtrues from 0.1 to 0.3). Women and older people tended to be lonelier, but these associations were entirely attributable to personality trait differences: once these were controlled for, the associations either reversed or became non-significant. Overall, we find that loneliness is far more closely related to Neuroticism than previously understood, and distinct from both social isolation and social disconnection.