Objective To explore the correlation between plasma oxidative stress markers and clinical symptoms as well as cognitive function in patients with depression. Methods Using a crosssectional study design， 87 inpatients with depression at Suzhou Guangji Hospital of Soochow University between May 2022 and May 2024 were selected to as depression group. During the same period， 75 healthy individuals from the local area， matched for age and gender， were recruited to as control group. The levels of total superoxide dismutase（ T-SOD）， catalase（ CAT）， total antioxidant capacity（ T-AOC）， hydrogen peroxide（ H2O2）， and hydroxyl radical（ ·OH） in the study subjects' plasma were measured. Cognitive function and the severity of clinical symptoms were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status（ RBANS）， Hamilton Depression Scale-24（ HAMD-24）， and Hamilton Anxiety Scale（ HAMA）. Pearson correlation was used to analyze the correlation between oxidative stress markers and scores on clinical psychological scales. Binary Logistic regression was used to examine the impact of oxidative stress markers on the risk of developing depression. Results The education years of depression group were lower than those of control group， and the difference was statistically significant（ t=-2.360， P ＜ 0.05）. The total score of RBANS（ t=-5.709， P ＜ 0.001） and the scores of immediate memory， visual span， verbal function， attention， and delayed memory in depression group were all lower than those in control group， with statistically significant differences（ t=-4.318， -3.484， -2.281， -5.100， -5.026； all P ＜ 0.05）. In depression group， plasma levels of T-SOD［ （77.94±4.65） U/ml vs.（ 79.88±3.21） U/ml］ and CAT［ （0.71±0.22） U/ml vs.（ 0.88±0.28） U/ml］ were lower than those in control group， and the differences were statistically significant（ F=3.193， 8.100； both P＜ 0.05）. In depression group， plasma levels of T-AOC ［（1.20±0.23） mmol/L vs.（ 1.10±0.10） mmol/L］， H2O2［ （55.08±20.94） mmol/L vs.（ 44.28±18.20） mmol/L］， and ·OH［ （438.19±137.02） U/ml vs.（ 221.39±53.05） U/ml］ were higher than those in control group， with statistically significant differences（ F=4.294， 5.270， 65.230； all P ＜ 0.05）. The HAMD-24 score was statistically negatively correlated with immediate memory scores， delayed memory scores， and the RBANS total score（ r=-0.345， -0.288， and -0.305； all P＜0.05）. The HAMA score was statistically negatively correlated with immediate memory scores， delayed memory scores， visual span scores， attention scores， and the RBANS total score（ r=-0.434， -0.412， -0.257， -0.261， -0.390； all P＜0.05）. Plasma T-SOD levels were statistically negatively correlated with HAMD-24 scores（ r=-0.288， P ＜ 0.05）. Multivariable logistic regression analysis showed that， when ·OH， T-AOC， and T-SOD were entered into the model simultaneously， higher ·OH levels were associated with increased odds of depression［ OR=1.003， 95%C（I 1.002-1.004）， P ＜ 0.001］， whereas higher T-AOC levels［ OR=0.329， 95%C（I 0.206-0.526）， P ＜ 0.001］ and higher T-SOD levels［ OR=0.977， 95%CI（0.960-0.995）， P=0.007］ were associated with lower odds of depression. Conclusions Patients with depression showed an imbalance between oxidant and antioxidant systems， characterized by reduced plasma T-SOD and CAT activities and higher levels of T-AOC， H2O2， and ·OH. T-SOD levels were associated with the severity of depressive symptoms， and greater clinical symptom severity was associated with poorer cognitive function. Multivariable logistic regression suggested that， after adjustment for the other oxidative stress markers included in the model， higher T-AOC and T-SOD levels were associated with lower odds of depression， whereas higher ·OH levels were associated with higher odds.