Mesial temporal sclerosis (MTS) is a severe form of temporal lobe epilepsy. Resection is the treatment of choice for refractory MTS but can still show seizure recurrence. We used seed-to-voxel analysis via amplitude synchronization to determine alterations in functional connectivity in MTS based on seizure-free status one year post-resection. Positive and negative correlations between temporal lobe structures and other brain regions were calculated and compared. We found changes in connectivity in MTS between ascending reticular activating system structures such as the thalamus and brainstem and temporal lobe structures. We also found differences in connectivity alterations between seizure-free and non-seizure-free patients.