Objectives: Adolescent e-cigarette use is an increasing public health concern in England, yet the psychosocial drivers of this trend remain poorly understood. This study examines the association between loneliness and current e-cigarette use among secondary school students aged 11–15. Methods: We analysed data from 13 725 pupils who participated in the 2023 wave of the nationally representative Smoking, Drinking and Drug Use among Young People in England survey. Loneliness was assessed using a validated composite score derived from 3 indirect questions on social isolation, categorised as low, medium, and high. Current e-cigarette use was defined as self-reported use “sometimes” or “every week.” Logistic regression models estimated crude and adjusted odds ratios (ORs) for the association between loneliness and vaping, adjusting for age, gender, current smoking, ethnicity, family affluence, and alcohol use. Results: Overall, 8.0% of adolescents (n=1104) reported current e-cigarette use. Compared with those reporting low loneliness, adolescents with medium and high loneliness had significantly greater odds of vaping, with adjusted ORs of 1.48 (95% confidence interval [CI], 1.24 to 1.76; p<0.001) and 2.46 (95% CI, 2.00 to 3.04; p<0.001), respectively. Findings were consistent in sensitivity analyses using weekly e-cigarette use as the outcome. Adolescents with medium and high loneliness had significantly higher adjusted odds of weekly use (adjusted ORs, 1.39; 95% CI, 1.11 to 1.75; p=0.005; and 2.04; 95% CI, 1.55 to 2.71; p<0.001, respectively) compared with those reporting low loneliness. Conclusions Loneliness is a strong and graded correlate of adolescent e-cigarette use.