The effects of social relations on mortality are complex and influenced by various factors. More specifically, both loneliness and social isolation have been linked to negative health outcomes and mortality. However, results in different studies are conflicting, and there is uncertainty whether there is a synergistic effect between social isolation and loneliness or not. In Sweden, living alone (a measure of social isolation) is common, especially among older adults, with implications for health. The present study aims to study the association between living alone and loneliness and all-cause and cause-specific mortality. The analysis will be conducted in a large combined cohort of women and men with a follow-up time of 15 years. The participants took part in the population-based cohort studies, the Swedish mammography cohort and the cohort of Swedish men. The study comprises 21 806 women and 26 006 men and study entry will be when participants completed the health questionnaire in 2008. The study will also explore information on general health, views on life, stress and well-being in association with loneliness, living alone and mortality. The study will contribute with important knowledge in a Swedish context, and may inform policy makers about important insights on the relationship between living alone, feeling lonely and mortality. This is important for public health in the context of a population where older adults are expected to remain in their homes, sometimes alone, due to age in place polices.