The coronavirus disease 2019 (COVID-19) pandemic has brought loneliness and related issues to the forefront of public awareness. Most people will have experienced some form of social isolation or loneliness during the repeated lockdowns and shielding requirements that were introduced to reduce the spread of infection. Mental health issues can also lead to loneliness and social isolation, while loneliness can produce similar signs and symptoms to mental health issues or exacerbate such issues. This article explores the concept of loneliness and its effects and describes how, in its most severe form, it can result in significant mental and physical harm. The article also considers what mental health practitioners, including nurses, can do to support people at risk of or experiencing loneliness.