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Suicides and suicidal behavior are major causes of mortality and morbidity in public health and are a global problem. Various authors have proposed changes in lipid metabolism (total cholesterol decrease) as a possible biological marker for suicidal behavior. The objective of this study was to review the studies that have demonstrated a relationship between serum cholesterol levels and suicidal behavior and to describe the possible pathophysiological mechanisms that associate changes in cholesterol concentration and suicidal behavior. Relevant literature related to serum cholesterol levels and suicidal behavior was identified through various database searches. The data from the existing literature present the findings that relate low cholesterol levels and possible pathophysiological mechanisms (neuroinflammation, serotonergic neurotransmission), genes related to cholesterol synthesis, pharmacological treatments that alter lipid metabolism and the possible participation in suicidal behavior. Nevertheless, future research is required to describe how serum cholesterol affects cholesterol metabolism in the CNS to establish and understand the role of cholesterol in suicidal behavior.