Flow paths and residence times in the hyporheic zone are known to influence biogeochemical processes such as nitrification and denitrification. The exchange across the sediment-water interface may involve mixing of surface water and groundwater through complex hyporheic flow paths that contribute to highly variable biogeochemically active zones. Despite the recognition of these patterns in the literature, conceptualization and analysis of flow paths and nitrogen transformations beneath riffle-pool sequences often neglect to consider bed form driven exchange along the entire reach. In this study, the spatial and temporal distribution of dissolved oxygen (DO), nitrate (NO₃^-) and ammonium (NH₄⁺) were monitored in the hyporheic zone beneath a riffle-pool sequence on a losing section of the Truckee River, NV. Spatially-varying hyporheic exchange and the occurrence of multi-scale hyporheic mixing cells are shown to influence concentrations of DO and NO₃^- and the mean residence time (MRT) of riffle and pool areas. Distinct patterns observed in piezometers are shown to be influenced by the first large flow event following a steady 8 month period of low flow conditions. Increases in surface water discharge resulted in reversed hydraulic gradients and production of nitrate through nitrification at small vertical spatial scales (0.10 to 0.25 m) beneath the sediment-water interface. In areas with high downward flow rates and low MRT, denitrification may be limited. The use of a longitudinal two-dimensional flow model helped identify important mechanisms such as multi-scale hyporheic mixing cells and spatially varying MRT, an important driver for nitrogen transformation in the riverbed. Our observations of DO and NO₃^- concentrations and model simulations highlight the role of multi-scale hyporheic mixing cells on MRT and nitrogen transformations in the hyporheic zone of riffle-pool sequences. This article is protected by copyright. All rights reserved.