SummaryA recently discovered neurodevelopmental disorder caused by the mutation of the cyclin‐dependent kinase‐like 5 gene (CDKL5) entails complex autistic‐like behaviours similar to Rett syndrome, but its impact upon physiological functions remains largely unexplored. Sleep‐disordered breathing is common and potentially life‐threatening in patients with Rett syndrome; however, evidence is limited in children with CDKL5 disorder, and is lacking altogether in adults. The aim of this study was to test whether the breathing pattern during sleep differs between adult Cdkl5 knockout (Cdkl5‐KO) and wild‐type (WT) mice. Using whole‐body plethysmography, sleep and breathing were recorded non‐invasively for 8 h during the light period. Sleep apneas occurred more frequently in Cdkl5‐KO than in WT mice. A receiver operating characteristic (ROC) analysis discriminated Cdkl5‐KO significantly from WT mice based on sleep apnea occurrence. These data demonstrate that sleep apneas are a core feature of CDKL5 disorder and a respiratory biomarker of CDKL5 deficiency in mice, and suggest that sleep‐disordered breathing should be evaluated routinely in CDKL5 patients.