The Illinois Department of Public Health confirmed it happened on Thursday while the bus was heading to the Chicago area.
A source familiar with the investigation and a Brownsville city spokesperson both told ABC News that the bus originated in Brownsville, Texas.
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"IDPH is working with local health officials, state police, and federal authorities to the fullest extent possible to get answers in this tragic situation," IDPH said in a statement.
There's no word yet on how the child died. Officials did not immediately provide further information.
ABC News contributed to this report.