Objective: To investigate the secretagogin (SCGN) plasma levels in children with autism spectrum disorder (ASD) compared to age and gender-matched healthy control, and its association with cognitive and social behaviors by using childhood autism rating scale (CARS) and social responsiveness scale (SRS). Study Design: Case-control study. Place and Duration of Study: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2015 to May 2016. Methodology: SCGN levels were determined in the plasma of thirty-seven (37) autistic children using enzyme-linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as indicated by their CARS scores and compared with thirty (30) age and gender-matched control samples. Correlation between SCGN levels and different cognitive and social behavior scales (CARS and SRS) was determined by Spearman's correlation coefficient (r). Results: The results indicated that autistic children (n=37) had significantly (p= 0.005) lower plasma level of SCGN {45.7 (26.2) ng/ml [median (IQR)]} than those of healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. Children with severe (n=28, 76%) as well as mild to moderate autism (n=09, 24%) also exhibited significantly lower SCGN levels {47.5 (27) ng/ml [median (IQR)], p =0.014} and {45.7 (16.6) ng/ml [median (IQR)], p = 0.02)}, respectively than healthy controls {n=30, 70.8 (48.6) ng/ml [median (IQR)]}. However, there was no significant difference between the SCGN levels of children with mild to moderate and severe autism (p = 0.66). Spearman's correlation coefficient (r) was used to determine the relationships between SCGN levels and different variables (CARS, SRS). However, the results showed no significant correlation between SCGN and these scales. (CARS, r=-0.03, p=0.86; SRS, r=0.21, p=0.20). Conclusion: The low SCGN plasma levels in children with ASD probably indicate that SCGN might be implicated in the pathogenesis of autism. However, these data should be treated with caution until further investigations are performed using larger sample sizes to determine whether the decrease in plasma SCGN levels is a mere consequence of autism or it plays a pathogenic role in the disease.