Objective: This systematic literature search aimed to investigate the physical health status of first-degree relatives to patients with bipolar disorder. There is abundant evidence for familial aggregation of both bipolar disorders, cardiovascular and autoimmune diseases. However, a review gathering data on the physical health status in first-degree relatives to patients with bipolar disorder is missing. We hypothesized that first-degree relatives of bipolar probands would express higher rates of physical diseases and somatic morbidity. Method: We conducted a systematic literature search in three different databases PubMed, Embase and PsychInfo. The search identified 10 studies comparing 24,277 unaffected first-degree relatives with 318.933 controls persons. Results: Seven out of 10 studies showed that first-degree relatives had statistically significantly higher rates of one or more physical diseases or increased morbidity, including cardiovascular diseases, infections, autoimmune thyroiditis, pernicious anaemia, and higher mortality compared with control persons. Conclusion: Findings from this systematic literature review did not unambiguously confirm a possible link between bipolar disorder and overall increased risk of physical diseases in first-degree relatives of probands with bipolar disorder. However, these results could suggest that first-degree relatives of probands with bipolar disorder could have a predisposition to poorer physical health than the general population and that this aspect warrants further investigation.