Numerous studies show the significance of immunological deficits, abnormal cytokine and immune cell production, and autism. Through the use of the childhood autism rating scale (CARS), the social responsiveness scale (SRS), and the computerized Cambridge neuropsychological test automated battery (CANTAB), the current study aimed to investigate the potential role of the autoimmune regulator protein AIRE-p as an immune biomarker in the pathophysiology of autism in Saudi children. According to the study's findings, plasma levels of AIRE-p in 37 autistic children (n=37) were considerably (p=0.003) lower than those in 37 healthy controls (n=37) at 0.629 (0.776) pg/ml [median (IQR)]. Based on CARS ratings, there was no difference between AIRE-p levels in children with mild to moderate autism (median, 0.661 (0.666) pg/ml; interquartile range, 0.365 (1.114) pg/ml; p = 0.365) and children with severe autism (median, 0.365 (1.114) pg/ml; interquartile range, 0.365). On the basis of SRS, a comparable pattern between mild to moderate and severe autism was also seen. AIRE-p may be involved in the physiology of autism as shown by the reduced AIRE-p plasma levels in patients with ASD. However, unless more studies are carried out using bigger sample sizes to ascertain if the drop in AIRE-p plasma level is only a side effect of autism or whether it plays a pathogenic role in the condition, these results should be viewed with care. If AIRE-p levels may be employed as a biomarker for ASD, further research including larger patient and control cohorts would be required.