A system comprises an implantable medical device configured to generate temperature data and impedance data associated with temperature and impedance of a patient proximate to the implantable medical device. The system further comprises processing circuitry configured to determine whether a first one or more infection criteria are satisfied by temperature data and impedance data generated by the implantable medical device during a first time interval, wherein the first one or more infection criteria include at least one criterion indicative of decreased impedance, determine whether a second one or more infection criteria are satisfied by the temperature data and impedance data generated by the implantable medical device during a second time interval subsequent to the first time interval, wherein the second one or more infection criteria include at least one criterion indicative of increased impedance, and output, based on satisfaction of the first and second infection criteria, an indication of infection.