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Although distinctive neuropsychological impairments have been delineated in children with chromosome 22q11 deletion syndrome (22q11DS), social skills and social cognition remain less well-characterised.To examine social skills and social cognition and their relationship with neuropsychological function/behaviour and psychiatric diagnoses in children with 22q11DS.Sixty-six children with 22q11DS and 54 control participants underwent neuropsychological testing and were administered the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) for face and auditory emotion recognition, a measure of social cognition: their parents/guardians were administered the Social Skills Rating System (SSRS) – parent version, Child Behavior Checklist (CBCL) – parent version and the Computerised Diagnostic Interview Schedule for Children (C-DISC).The 22q11DS group exhibited significantly lower social skills total score and more problem social behaviours, lower neurocognitive functioning, higher rates of anxiety disorders and more internalising symptoms than the control group. Participants with 22q11DS also exhibited significant deficits in their ability to read facial expressions compared with the control group, but performed no differently than the control participants in the processing of emotions by tone of voice. Within the 22q11DS group, higher social competency was correlated with higher global assessment of functioning and parental socio-economic status. Social competency was worse in those with anxiety disorders, attention deficit hyperactivity disorder, more than two psychiatric diagnoses on the C-DISC and higher internalising symptoms. No significant correlations of SSRS scores were seen with IQ, executive functions, attention, or verbal learning and memory. No correlations were found between social cognition and social skill scores.Our results indicate that social skills in children with 22q11DS are associated with behaviour/emotional functioning and not with neurocognition. Thus, treating the behaviour or emotional problems such as attention deficit hyperactivity disorder and anxiety disorders may provide a pathway for improving social skills in these children.