The aim of the present study was to identify a cut-off of c-reactive protein (c-RP) potentially predictive of high-lethality suicide attempts (SA) in an inpatient psychiatric sample. After attempting suicide, subjects were admitted to the emergency ward of the IRCCS Ospedale Policlinico San Martino and later to the section of Psychiatry from 1 August 2013 to 31 July 2018. C-reactive protein was measured. The Area Under the Receiver Operating Characteristic (ROC_AUC) was used to assess the discriminative capacity of c-RP for high- vs. low-lethality SA, and a logistic regression was performed to detect the odds ratio, adjusted for age and sex. High-lethality suicide attempters were 133 (30.8%), while low-lethality suicide attempters were 299 (69.2%). The optimal cut-off threshold (and corresponding sensitivity and specificity values) for c-RP was 4.65 mg/L (68/71%). This cut-off corresponds to an AUC of 73.5%. An odds ratio of 4.70 was generated for current high-lethality SA after a logistic regression, adjusted for age and sex. Research on social and biological factors underlying the lethality of SA is crucial for a better understanding of this complex phenomenon. Identifying potential predictors of SA, especially those at high lethality, is essential to implement personalized preventive strategies.