Mounting evidence points to an up-regulated inflammatory response in patients who experience suicidal ideation, attempt, or commit suicide. Translational and clinical studies are now disentangling the neurobiological mechanisms that generate the symptoms in inflammation-induced depression. But what are the actual causes of the low-grade, long-term inflammation that is observed in the patients? The triggers and root causes of this enigmatic inflammation are not yet well studied. In this issue of JAMA Psychiatry, Lund-Sørensen et al1 show that severe infections are associated with increased suicide risk. In this large epidemiological study following up more than 7 million Danish citizens for 30 years (approximately 150 million person-years), the authors found that the risk of death by suicide is increased by more than 40% in individuals who have had hospital contacts for infections. Strengthening the case for a possible causal role of infections in the pathogenic process that leads to suicide, these researchers show that an increased risk of suicide was associated with the length of treatment and with an increasing number of hospitalizations with infections. Individuals with 7 or more infections had an increased risk for suicide of almost 300%.