Abstract Background Studies have shown that the presence of pediatric mental disorders causes great impairment in academic, social, and professional activities as well as in the quality of life (QoL) of the patients as well as their caregivers. Aim of the Work Compare the health related quality of life (HRQoL) scores of children with pediatric mental disorders and their caregivers to those of apparently healthy children of comparable sex and age. Patients and Methods This was an observational study that included seventy-five (75) children with various pediatric mental disorders of different diagnoses (25 cases ASD, 25 cases nocturnal enuresis, 25 cases ADHD) represented the patient group (1). They were 25 females and 50 males. Their ages ranged between 4–15 years with mean ± SD of 9.32 ± 4.72 years. Another 25 healthy children matched in age and sex with the patients’ group (1) were selected as a control group (2). Results Caregivers of children with ASD, nocturnal enuresis and ADHD had an elevated risk of experiencing mental health problems. Children with ASD, enuresis and ADHD have a higher risk for additional behavioral problems tested by Pediatric Symptom Checklist, Child Behavior Checklist and DSM-V. Female cases, in all subgroups, had lower scores than male cases in the three subgroups regarding PSC and CBCL of attention, internalizing and externalizing subscales; however, results didn’t reach level of significance Conclusion Children with ASD, enuresis and ADHD and their caregivers have a higher risk for additional behavioral problems than children without mental disorders.