A quantitative approach for the evaluation of the organic matter transport across the bed-water interface, in rivers characterized by organic-rich beds, was derived and implemented, in order to capture the additional oxygen demand in the water column associated with the resuspension of organic sediments from the bottom. Through the coupling of hydrodynamics, sediment transport and water quality, the process was described in terms of its dependency on the properties of the flow, the sediments and the bed. This approach represents a substantial improvement to the state-of-the-art water quality modeling methodologies and was applied to the scenario of Combined Sewer Overflow (CSO) discharge for the case of Bubbly Creek, which is the South Fork of the South Branch of the Chicago River. The modeling allowed for capturing the Dissolved Oxygen (DO) depletion following the CSO discharge, which is due to the CSO input but mainly due to the organic matter resuspended from the bottom of the creek. The methodology presented was also able to model the key processes and to correctly estimate the DO dynamics observed during and few days after the historic CSO event considered.