This study aimed to determine the impact on the lipid profile, carboxypeptidase N (CPN) and nitric oxide (NOx) associated with vitamin D (VD) status correction among Saudi adults with VD deficiency. A total 111 VD deficient (25(OH)D < 50 nmol/L)) adult Saudis aged 18–50 years old (57 females and 54 males) were enrolled in this 6-month interventional study. They were given 50,000 IU VD weekly for the first 2 months and then twice a month for the next 2 months, followed by 1000 IU daily for the last 2 months. The fasting lipid profile and the blood glucose, VD, NOx and CPN concentrations were measured at baseline and after intervention. Post-supplementation, the median VD was significantly higher (p< 0.001) in females [58.3 (50.6–71.2)] and males [57.8 (51.0–71.8)]. HDL cholesterol significantly increased (p= 0.05) and NOx significantly decreased (p= 0.02) in males post-supplementation. Triglycerides were positively associated with NOx in all subjects before (r = 0.44,p= 0.01) and after (r = 0.37,p= 0.01) VD status correction. There was a significant increase in serum levels of CPN2 (p= 0.02) in all subjects. Furthermore, CPN was inversely correlated with NOx (r = −0.35,p= 0.05) in males post-supplementation. In conclusion, VD status correction reduced serum NOx, particularly in males. The inhibition of NOx synthesis may be responsible for the anti-inflammatory effects of VD supplementation. An inverse association was found between NOx and CPN2.