<p>The 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder frequently associated with schizophrenia, whose study could shed light on the neurophysiological basis of psychotic risk and disease onset. We tested the hypothesis of a disrupted resting-state in electroencephalography (EEG), which we expected to be more perturbed in 22q11.2DS with schizophrenia relative to those without, and to controls. We retrospectively included 39 individuals (11 controls, 12 22q11.2DS, and 16 22q11.2DS with schizophrenia) with available routine EEG, who were compared for: (1) power spectral density (PSD) and the relative PSD alpha peak; (2) connectivity, based on the weighted phase lag index, and the relative global connectivity alpha peak; (3) microstates, described by their occurrence, temporal coverage, and mean duration. Microstates were built on controls and applied on the 22q11.2DS groups, which were compared with each other. We observed that 22q11.2DS with schizophrenia showed an increase in theta PSD (<i>p</i> = 2e⁻⁴), a decrease in average relative alpha power (<i>p</i> = 0.04) and global connectivity (<i>p</i> = 0.03), compared to healthy controls, while 22q11.2DS without schizophrenia had values between the controls and the subjects with 22q11.2DS and schizophrenia, with no significant differences with either groups. Microstate analysis found a significant increase in class C in patients with schizophrenia compared to those without (<i>p</i> = 0.045). These group-level neurophysiological anomalies may be present across the clinical trajectory, from genetic risk to chronic disease in 22q11DS, suggesting a potential relevance for a staging approach to early intervention in psychiatry.</p>