Brain temperature is a vital physiological parameter that has a great effect on metabolic processes, enzymatic activity, neurotransmitter function, blood flow regulation, neuroprotection, and cognitive performance. In this framework, the development of accurate and reliable brain temperature measurement tools is crucial in brain-related treatment and research, such as neurosurgery, therapeutic hypothermia, and the understanding of brain function and pathologies. Here, we developed the first large-core flexible low optical loss CYTOP polymer optical fiber (POF)-based brain temperature probe operating in the telecommunication spectral range. The temperature measurements were achieved by detecting the reflected spectrum from a fiber Bragg grating (FBG) directly inscribed at the tip of the POF using femtosecond pulses. A fluorinated ethylene propylene (FEP) tube was thermally drawn and used as a sleeve around the FBG structure to eliminate the cross-sensitivity with humidity and microstrain perturbations. The assembled POF implant has a sensitivity of 14.3 pm/°C. The local temperature of the cerebral cortex, corpus callosum, and striatum in a rat brain was measured in vivo. The results indicate that the deep brain regions have higher temperature than the top cortical ones with a relatively linear relationship between the brain structure depth and its temperature. In addition, the rectal body core temperature was detected in parallel with the brain temperature measurement to further validate the developed device. We believe that the presented CYTOP POF-based implantable temperature probe opens the way towards the development of flexible and stable tools for accurate brain temperature recording where large-core fiber-based neural devices are required.