INTRODUCTION Autism is a worldwide disorder 1 defined as severe psychiatric disorder of childhood marked by severe difficulties in communication and forming relationships with other people, in developing language, repetitive, and limited patterns of behaviors and obsessive resistance to small changes in familiar surroundings. 2 These signs all begin in children before the age of 3 years. 3 It affects information processing in the brain by altering how nerve cells and their synapses connect and organize; however, how this occurs is not well understood. 4 There are three recognized disorders in the autism spectrum (ASDs), first is the autism disorder and the other two are Asperger syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). 5 Prevalence of ASD ABSTRACT Background: This study aimed to evaluate the presence of depression in a group of mothers of ASD children in comparison with a group of mothers of normally developing children and to identify associated factors. Methods: A case control study design, 60 autistic cases diagnosed by DSM-IV-TR criteria (American psychiatric association, 1994 diagnostic and statistical manual of mental disorders, 4 th edition criteria, text revised) were recruited from Mental health clinic of Children Hospital Taif Region KSA, and private autism center, these cases with their parents were enrolled in the group called (cases). One control subject was matched for each case in the age of mother, sex and age of the patients, they were recruited from well-baby clinic of children hospital. These cases with their mothers were enrolled in the group called (controls). Results: Using short Beck inventory scale depression was significantly more among cases than controls (P = 0.001, 0.001, 0.000). Exploring socio-demographic factors while female sex had a significant impact on maternal depression (P =0.022), number of siblings, family income, level of mother education, showed no significant impact on maternal depression (P = 0.72, 0.53, 0.71). Considering factors related to autism, the only significant factor was the mean age of autism child (P = 0.022). In relation to the support factors, while mother knowledge about autism, mother joining a support group had no significant impact on maternal depression (P =0.35, 0.44) the social and financial support for autistic families were both significantly impacting maternal depression (P =0.02, 0.001). Conclusions: Autism is associated with burden and stress for mothers of the affected child. The demands placed by disability contribute to higher overall incidence of depression among mothers. Mothers of ASD children do need psychological interventions. Evaluate the efficacy of support group in local community. Stress on social support to mothers Of ASD children as it had a significant impact on maternal depression.