**Abstract** Humans are a highly socially interdependent species, making social cues an important input for allostatic systems that protect the body from harm and conserve energetic resources, such as those involved in threat sensitivity and negative affect. Research in clinical populations has associated perceived social isolation with a co-occurring set of symptoms (henceforth, symptom cluster) marked by increased pain, fatigue, and depression. Although not directly on the symptom cluster, other research has shown that pain and depression are more common in individuals with low socioeconomic status. Research also suggests that supportive social relationships are especially important for buffering the negative health effects of low socioeconomic status, but that feelings of social disconnection may be exacerbated by the difficulties of living in poverty. Thus, loneliness may be more common in individuals with lower incomes, and the symptom cluster may be most prevalent in individuals who are both lonely and in poverty. This study is the first to investigate associations amongst poverty, loneliness, and this symptom cluster in a multinational, general population sample (*n* = 24,805). We show that those from lower income deciles are much more likely to feel lonely, despite no differences in reported time spent socialising. Lonely individuals also score higher on the symptom cluster, and as income increases, scores on the symptom cluster decrease. Finally, we show that the association of loneliness with the symptom cluster is stronger amongst those on lower incomes. We discuss how these findings can inform understandings of social and economic gradients in health outcomes.