Purpose: To compare the aqueous humor (AH) and serum levels of 4-hydroxynenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OhdG) in patients with pseudoexfoliation syndrome (PES) and pseudoexfoliation glaucoma (PEG) with each other and with age- and sex-matched control group. Methods: This prospective study included 66 patients divided into three groups: PES (n = 24), PEG (n = 21), and a control group (n = 21). 4-HNE and 8-OhdG levels were analyzed using the enzyme-linked immunosorbent assay. Results: Aqueous and serum 4-HNE levels were significantly higher in the PEG (466.52 ± 62.12 pg/mL and 313.47 ± 47.41 pg/mL) and PES (290.69 ± 63.63 pg/mL and 201.53 ± 39.57 pg/mL) groups than the control group (144.02 ± 39.58 pg/mL and 99.10 ± 16.96 pg/mL; p < 0.001, for all). Both aqueous and serum levels of 4-HNE in the PEG group were significantly higher than in the PES group (p < 0.001, for both). Similar to 4-HNE, the AH 8-OhdG levels were higher in the PEG group (21.18 ± 2.23 ng/mL) compared to the PES (14.90 ± 3.37 ng/mL) and control (4.86 ± 1.94 ng/mL) groups (p < 0.001, for all). Serum 8-OhdG levels were significantly higher in the PEG and PES groups than the control (p < 0.001, for both); however, there was no significant difference between the PES and PEG groups (p = 0.097). There were strong significant correlations between the aqueous and serum levels of 4-HNE (p < 0.001, r = 0.857) and 8-OhdG (p < 0.001, r = 0.807) among all the patients. Conclusions: Aqueous humor and serum levels of 4-HNE and 8-OhdG increased in the PES and PEG patients. These findings are potentially significant and add to the growing body of evidence concerning oxidative stress in PES and PEG.