Cocaine-related mortality rates have risen sharply since 2013 and social vulnerability is a crucial indicator for drug-related mortality rates. Therefore, the purpose of this study was to investigate the relationship between social vulnerability and cocaine-related mortality rates in U.S. counties. The Data were collected from the CDC WONDER, CDC's Social Vulnerability Index (CDC's SVI), and American Community Survey (ACS). The Data were analyzed by spatial autoregression models. According to present results, first, counties with social vulnerability (socioeconomic) were positively related to higher rates of cocaine overdose death (spatial lag: B = 0.323, p < .05; spatial error: B = 0.513, p < .01). Second, counties with social vulnerability (minority status & language) were negatively related to higher rates of cocaine overdose death (spatial lag: B = -0.233, p < .05). Third, counties with social vulnerability (housing type & transportation) were positively related to higher rates of cocaine overdose death (spatial lag: B = 0.413, p < .001; spatial error: B = 0.378, p < .001). In conclusion, the spread of cocaine overdose on U.S. counties with social vulnerabilities demonstrated a disproportionate burden of cocaine-related mortality.