Previous studies in small-cell lung cancer (SCLC) patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI). Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN), the Sensorimotor Network, and the Task-Positive Network (TPN). Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations.