This chapter summarizes why there is an interest in exploring the relationship between social isolation and loneliness with inflammation. It starts by discussing different theories that explain how loneliness and social isolation could lead to inflammation and inflammation to loneliness and social isolation. Next, it summarizes existing evidence on the association between loneliness and social isolation with inflammation. We also critically consider the issues with the existing evidence base. Finally, we consider whether inflammation acts as a mediator in the relationship between loneliness and social isolation with poorer health.