Data on the effects of selenium (Se) supplementation on clinical outcomes, metabolic profiles, and pulsatility index (PI) in high-risk mothers in terms of preeclampsia (PE) screening with quadruple tests are scarce. This study evaluated the effects of Se supplementation on clinical outcomes, metabolic profiles, and uterine artery PI on Doppler ultrasound in high-risk mothers in terms of PE screening with quad marker. The current randomized, double-blind, placebo-controlled trial was conducted among 60 high-risk pregnant women screening for PE with quad tests. Participants were randomly allocated into two groups (30 participants each group), received either 200 µg/day Se supplements (as Se amino acid chelate) or placebo from 16 to 18 weeks of pregnancy for 12 weeks. Clinical outcomes, metabolic profiles, and uterine artery PI were assessed at baseline and at the end of trial. Se supplementation resulted in a significant elevation in serum Se levels (β 22.25 µg/dl; 95% CI, 18.3, 26.1;
P
< 0.001) compared with the placebo. Also, Se supplementation resulted in a significant elevation in total antioxidant capacity (β 82.88 mmol/L; 95% CI, 3.03, 162.73;
P
= 0.04), and total glutathione (β 71.35 µmol/L; 95% CI, 5.76, 136.94;
P
= 0.03), and a significant reduction in high-sensitivity C-reactive protein levels (β − 1.52; 95% CI, − 2.91, − 0.14;
P
= 0.03) compared with the placebo. Additionally, Se supplementation significantly decreased PI of the uterine artery in Doppler ultrasound (β − 0.09; 95% CI, − 0.14, − 0.04;
P
= 0.04), and a significant improvement in depression (β − 5.63; 95% CI, − 6.97, − 4.28;
P
< 0.001), anxiety (β − 1.99; 95% CI, − 2.56, − 1.42;
P
< 0.001), and sleep quality (β − 1.97; 95% CI, − 2.47, − 1.46;
P
< 0.001). Se supplementation for 12 weeks in high-risk pregnant women in terms of PE screening with quad marker had beneficial effects on serum Se level, some metabolic profiles, uterine artery PI, and mental health. IRCT Registration: htpp://
www.irct.ir
; identifier IRCT20200608047701N1.