Brain network alterations have been studied extensively in patients with mesial temporal lobe epilepsy (mTLE) and other focal epilepsies using resting-state functional magnetic resonance imaging (fMRI). However, little has been done to characterize the basic fMRI signal alterations caused by focal epilepsy. Here, we characterize how mTLE affects the fMRI signal in epileptic foci and networks. Resting-state fMRI and diffusion MRI were collected from 47 unilateral mTLE patients and 96 healthy controls. FMRI activity, quantified by amplitude of low-frequency fluctuations, was increased in the epileptic focus and connected regions in mTLE. Evidence for spread of this epileptic fMRI activity was found through linear relationships of regional activity across subjects, the association of these relationships with functional connectivity, and increased activity along white matter tracts. These fMRI activity increases were found to be dependent on the epileptic focus, where the activity was related to disease severity, suggesting the focus to be the origin of these pathological alterations. Furthermore, we found fMRI activity decreases in the default mode network of right mTLE patients with different properties than the activity increases found in the epileptic focus. This work provides insights into basic fMRI signal alterations and their potential spread across networks in focal epilepsy.