Seizures in temporal lobe epilepsy (TLE) disturb brain network physiology and lead to brain connectivity disturbances. We used resting-state functional MRI (fMRI) recordings in TLE patients and controls to examine functional connectivity between brainstem ARAS structures and cortical/subcortical regions. ARAS connectivity was significantly lower in TLE patients than controls, with largest connectivity decreases noted in neocortical regions ipsilateral to the epileptogenic zone. Diminished ARAS connectivity was related to seizure frequency and neuropsychological impairments. Functional connectivity analysis of small brainstem structures using fMRI is feasible and may provide important information regarding mechanisms of disease in neurological disorders.