Analysis of dissolved organic carbon (DOC) is widely used to quantify the sum of organic carbon species in water. Analyzers based on wet chemical oxidation (WCO) usually have a relatively low detection limit (±1 μg of C/L) and are, therefore, well suited for analyses of DOC in environmental samples (e.g., surface water, groundwater, or seawater). However, these matrices might contain relatively high concentrations of chloride that can affect the DOC oxidation efficiency. We validated the DOC analysis using a combined persulfate and ultraviolet oxidation method in various prepared samples (humic and fulvic acids and selected organic acids) with different background concentrations of chloride. The results show that chloride is an effective radical scavenger (at concentrations of >355 mg of Cl–/L) that reduces the oxidation efficiency of DOC analyses based on WCO. The oxidation efficiency correlates well with the proton dissociation constant of the selected organic acids. Our findings imply that the DOC analyses by WCO methods should include an assessment of the chloride concentrations in the samples to check for potential interference. The results are relevant for DOC analysis in samples containing high background levels of chloride (e.g., brackish water) and for samples from DOC fractionation methods to quantify humic substances.