Context: Carbon monoxide (CO) poisoning results in neuronal injury. The expression of Dickkopf-1 (DKK-1) has not been investigated previously after CO poisoning.Objective: The current study aimed to investigate the DKK-1 expression levels in humans and rats with acute CO poisoning and to analyze their correlation with poisoning severity.Materials and methods: We measured serum DKK-1 levels in patients with acute CO poisoning (n=94) and in healthy controls (n=90). On admission, a poisoning severity score (PSS) was determined for each patient. In addition, 36 male Sprague-Dawley rats were randomly assigned into three groups: (a) Sham group, (b) Low CO group and (c) High CO group. At 2h after CO poisoning, DKK-1 expression and histopathological damage in the hippocampal tissues were measured.Results: Serum DKK-1 levels were significantly higher in the acute CO-poisoned patients, compared to the healthy controls. Serum DKK-1 levels were significantly higher in the CO-poisoned patients with a lower PSS. In rats, CO poisoning induced significant upregulation of the gene and protein expression of DKK-1 in hippocampal tissues. Moreover, there was a positive correlation between DKK-1 levels and the degree of damage in the hippocampal tissues.Discussion: DKK-1 induction in neurons after CO poisoning causes further neuronal injury. The severity of acute CO poisoning in rat models is associated with elevated serum DKK-1 levels and its upregulation in the brain tissue.Conclusion: DKK-1 appears to have potential utility in providing valuable information for determining the severity and damage of CO poisoning.