The child was found unresponsive when police were called to a home in the 800 block of Oak Street Tuesday night.
According to police, the child appears to have been malnourished and has injuries consistent with child abuse.
The girl was given CPR at the scene and rushed to Mercy Hospital, but was later pronounced dead.
A man and woman in their 20s are now being held in connection with the child's death.
The St. Clair County Prosecutor's office will review the case before charges can be filed.
Three other children were removed from the home, one of whom was also taken to the hospital for treatment for malnutrition. The other two have been placed in foster care.
An autopsy for the 5-year-old girl is scheduled for Tuesday afternoon.
This is a developing story. Stay with FOX 2 for updates.