BACKGROUND:People with Autism Spectrum Disorder (ASD) are at significantly increased risk of suicidal thoughts and behavior. Given that social difficulties in ASD often lead to social isolation, which can in turn increase the risk for depression, this study examined loneliness and social support as potential risk and protective factors associated with depression and suicidal ideation. METHOD:The sample comprised 185 people (92 females) with ASD aged 14 to 80 years who were participating in a national survey. RESULTS:Forty-nine percent of participants returned scores in the clinical range for depression and 36% reported recent suicidal ideation. Females, comprising almost 50% of the sample, returned higher depression scores than males, however no differences were identified between males and females in terms of suicidal ideation. Regression analyses revealed that loneliness, satisfaction with social support, and ASD traits predicted depression scores. Satisfaction with social support predicted suicidal ideation, however, it was no longer a significant predictor after the effects of depression were taken into account. Path analysis showed that ASD trait severity was independently related to depression, that the effect of number of social supports on depression was mediated by loneliness and satisfaction with social support, and that effects of loneliness and satisfaction with social support on suicidal ideation were mediated by depression. The pattern of relationships was nearly identical for males and females. CONCLUSIONS:This study supports a model whereby loneliness and social support operate respectively as protective and risk factors for depression and suicidal ideation in ASD.