OBJECTIVE: Deep brain stimulation (DBS) is emerging as a promising therapy for patients with drug-resistant epilepsy, particularly those who are either unsuitable for or unresponsive to resective surgery. The potential benefit of DBS in these patients may stem from its ability to reduce excessive brain functional connectivity (FC). Given that patients undergoing presurgical evaluation in our institution are implanted with stereoelectroencephalographic (SEEG) electrodes in the thalamus, specifically in the pulvinar medialis (PuM), our aim was to investigate the impact of different stimulation frequencies on brain FC. We sought to determine whether specific frequencies were more effective in modulating FC. METHODS: SEEG was used to investigate the effects of PuM stimulation across a broad frequency range (1-200 Hz) in a cohort of 14 patients with drug-resistant focal epilepsy. FC was assessed using the nonlinear correlation coefficient (h) and node strength calculations. RESULTS: Our findings revealed a reduction in FC at stimulation frequencies of 10 Hz and >90 Hz, contrasting with an increase in FC in the 20-80-Hz range. This modulation of FC extended beyond the epileptogenic zone, influencing all assessed brain lobes, with the parietal, insular, and subcortical regions particularly affected by high-frequency stimulation. Within the epileptogenic zone, however, the observed FC changes were notably more complex. SIGNIFICANCE: These results underscore the potential of high-frequency stimulation to decrease interictal FC in epilepsy patients, although intermediate frequencies may exacerbate it and warrant caution. Crucially, this study highlights the effects of PuM stimulation on FC patterns, supporting the role of high-frequency thalamic stimulation as a promising DBS parameter for improving epilepsy management strategies.