This brief presents results from a statistical analysis examining the relationship between indicators of substance use prevalence and child welfare caseloads. The analysis used data on child welfare caseload rates and indicators of substance use prevalence from 2011 through 2016 for most U.S. counties. The study found that nationally, rates of drug overdose deaths and drug-related hospitalizations have a positive relationship with child welfare caseload rates, after accounting for county socioeconomic and demographic characteristics. These substance use indicators correlate with rates of more complex and severe child welfare cases. Increases in rates of overdose deaths and drug-related hospitalizations are associated wwith a higher proportion of children entering foster care after reports of child maltreatment. Opioid-related hospitalization rates have a relationship with caseload rates comparable to that of other substance types, though alcohol has a stronger relationship than any illicit or prescription substance. Although there is a positive association between the substance use measures and child welfare caseload rates, this association cannot be positively identified as causal. Substance use, including opioid misuse, has downstream effects on childrens welfare and family stability, and these in turn can place a substantial burden on communities. (Author Abstract Modified)