© 2021Objective: Oligohydramnios is defined as amniotic fluid index in ultrasonographic measurement is less than 5 percentile according to gestational age, the amniotic fluid volume is ≤ 5 cm, or if the single deepest dial is < 2 cm. The condition of oligohydramnios that not with fetal structural/chromosomal abnormalities, intrauterine growth retardation, intrauterine infection and maternal disease is described as isolated oligohydramnios (IO). The aim of this study is to examine whether oxidative stress and reactive oxygen species (ROS) have a place in the pathophysiology of IO. Materials and methods: In this prospective case–control study, a total of 126 participants were included. The patient group consisted of 65 patients who were diagnosed IO, and the control group consisted of 61 healthy normal pregnants. Native thiol (-SH), total thiol (-SH + -SS), dynamic disulfide (-SS), IMA values from maternal serum were measured and compared between groups. Results: Maternal serum -SH and -SH + -SS values were significantly lower in the IO group than in the control group (409.47 ± 55.36 μmol/L vs. 437.40 ± 48.68 μmol/L, p = 0.03 and 457.40 ± 63.01 μmol/L vs. 484.59 ± 52.75 μmol/L, p = 0.01). In the IO group when -SS/-SH and -SS/-SH + -SS ratio was found to be statistically significantly higher than control group (5.84 ± 1.1 vs 5.41 ± 0.71, p = 0.01 and 5.2 ± 0.88 vs 4.8 ± 0.58, p = 0.01), -SH/-SH + -SS ratio was significantly lower (89.56 ± 1.7 vs 90.24 ± 1.16, p = 0.01). There was no significant difference in terms of -SS value (p = 0.66). IMA value was significantly higher in the IO group than control group (0.76 ± 0.10 ABSU vs 0.68 ± 0.06, p < 0.01). It is seen as a result of ROC analysis that -SH, -SH + -SS, -SS/-SH, -SS/-SH + -SS, -SH/-SH + -SS and IMA values have a diagnostic value for IO (p < 0.05). Conclusion: The thiol/disulfide balance shifted towards oxidative stress in IO compared to control group. So oxidative stress and ROS have a place in the pathophysiology of IO.