In this paper, we present a flexible temperature sensor with ultra-small polysilicon thermistors for brain temperature monitoring. In vitro sensitivity, resolution, thermal hysteresis and long term stability tests were performed. Temperature coefficient of resistance (TCR) of −0.0031/ °C and resolution of 0.1 °C were obtained for the sensor. Thermal hysteresis for temperature range of 30∼45 °C was less than 0.1 °C. With silicon nitride as the passivation layer, the temperature sensor showed a drift within 0.3 °C for 3 days long term stability test in water. In vivo tests showed a clear correlation between the localized brain temperature and electrocorticography (ECoG) signal during spreading depolarization. The developed flexible temperature sensor with small size polysilicon thermistors can be adopted for high resolution brain temperature mapping as well as multimodal monitoring with limited sensing space.