A growing number of studies suggest that social isolation and loneliness are associated with general morbidity and premature mortality [
1,
2] and are more prevalent among people with severe mental illness than in the general population [
3], outlining many potential paths to disease [
4‐
7]. Loneliness has been described as the distressing subjective experience of lacking relationships or missing a certain level of quality in them [
8]. Social isolation, on the other hand, concerns the objective characteristics of one’s relationships and refers to shortcomings in the size of their social network [
9]. Although the relationship between loneliness and social isolation is complex [
9], both have been associated with mental health and cardiometabolic disease and mortality [
10], particularly among the elderly. Furthermore, although people with severe mental illness (SMI) experience high levels of both loneliness [
11,
12] and cardiometabolic disease [
13], little is known about the relationship between loneliness and social isolation and cardiometabolic health in patients with SMI, and to which degree such associations may be related to the reduced life expectancy in patients with SMI [
13,
14]. Thus, a better understanding of the relationships between loneliness and social isolation and cardiometabolic health is needed, both in the general population and in patients with SMI. To this end, we will conduct a meta-analysis of studies on loneliness, social isolation, and their associations with cardiovascular and metabolic risk, building on the methodology of a previous systematic review and meta-analysis of the role of social isolation and loneliness as risk factors for coronary heart disease and stroke [
15]. Compared to the previous publication [
15], the present meta-analysis has a broader scope by looking at more general cardiometabolic conditions, including risk factors and some diseases of the cardiovascular system, as well as a special attention to SMI.