Background: Loneliness is a significant public health concern and a well-established social determinant of health, affecting both mental and physical well-being. It has been linked to an increased risk of depression, anxiety, cardiovascular disease, and premature mortality. Despite growing awareness, loneliness remains an underrecognized and undertreated factor influencing population health. Objective: This study examines the impact of loneliness on the likelihood of being diagnosed with depression, as well as its association with self-reported poor mental and physical health days. Methods: Data were analyzed from the Behavioral Risk Factor Surveillance System (BRFSS) (2016–2023). The primary exposure was self-reported loneliness, captured through the question, "How often do you feel lonely?" with responses ranging from "Always" to "Never." Main outcomes included depression diagnosis, poor mental health days, and poor physical health days. Covariates included age, race, gender, marital status, education, employment, state, year, metropolitan status, and language spoken at home. Inverse Probability Weighting (IPW) was used to estimate the Average Treatment Effect (ATE), accounting for confounders and state and year fixed effects. Sampling weights ensured national representativeness, and robust standard errors accounted for clustering by state. Results: Among 47,026 participants, 82.4% reported experiencing some degree of loneliness, with 6.2% feeling "Always" lonely, 8.3% feeling "Usually" lonely, 37.9% feeling "Sometimes" lonely, and 29.9% feeling "Rarely" lonely. In contrast, 17.7% of participants reported "Never" feeling lonely. For further analysis, 2,609 individuals who reported feeling lonely were matched with 2,609 individuals who reported "Never" feeling lonely", forming a balanced comparison group. The "Always Lonely" population was predominantly White (64.5%) and female (55.0%), with the majority aged 45–64 years.  Loneliness was significantly associated with an increased likelihood of depression diagnosis, with a 39.3% percentage-point increase for those reporting Always lonely (ATE = 0.39, 95% CI: 0.34–0.44, p < 0.001). Loneliness was also associated with a 10.9-day increase in poor mental health days (ATE = 10.9, 95% CI: 9.8–11.9, p < 0.001) and a 5.0 day increase in poor physical health days (ATE = 5.0, 95% CI: 3.8–6.1, p < 0.001). Conclusions: Loneliness is a strong predictor of depression and poor mental and physical health. Interventions addressing social isolation could mitigate the negative health impacts associated with loneliness, improving population health outcomes.

The authors have declared no competing interest.

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