Multimorbidity has been linked to a variety of negative outcomes although as yet, there has been little research on its association with loneliness. This study examined the association between physical multimorbidity (≥ 2 physical diseases) and loneliness in the general population and its potential mediators. Data came from the Adult Psychiatric Morbidity Survey 2007 (N = 7403, aged ≥16 years). Information was obtained on 20 doctor diagnosed physical conditions that were present in the previous year. An item from the Social Functioning Questionnaire (SFQ) was used to obtain information on loneliness. Multivariable logistic regression analysis was used to examine associations. An increasing number of physical diseases was associated with higher odds for loneliness. Compared to no physical diseases, the odds ratio (OR) (95% confidence interval: CI) for loneliness increased from 1.34 (1.13-1.59) to 2.82 (2.11-3.78) between one and ≥5 physical diseases. This association was particularly strong in the youngest age group (i.e. 16-44 years). The loneliness-physical multimorbidity association was significantly mediated by stressful life events (% mediated 11.1%-30.5%), anxiety (30.2%), and depression (15.4%). Physical multimorbidity is associated with increased odds for loneliness. Prospective research is now needed to further elucidate this association and the factors that underlie it.