Loneliness and social isolation, accompanied by recent changes in social structure, have garnered significant attention as major social problems, prompting an urgent need for immediate solutions. Both are issues that occur among healthy individuals and are also significant symptoms for patients with mental disorders characterized by social withdrawal, such as schizoid personality disorder and hikikomori (known as a pathological social withdrawal syndrome, originally in Japan). They are not only viewed as mental afflictions but also as sources of adverse physical effects, rooted in certain biological mechanisms. In this context, it would be beneficial to examine two disorders that share common traits of avoiding social interactions and living socially isolated lives: schizoid personality disorder and hikikomori. Biological studies of both disorders have indicated a potential association between low serum LDL cholesterol levels and experiences of loneliness and social isolation. Moreover, differences in the distribution of certain molecular species of cholesterol ester have been observed in the blood of hikikomori patients compared to healthy individuals. Further research focusing on lipids is anticipated to provide insights into the biological basis of loneliness and social isolation.