Sediment–water fluxes are influenced by both hydrodynamics and sediment biogeochemical processes. However, fluxes at the sediment–water interface (SWI) are almost always analyzed from either a water- or sediment-side perspective. This study expands on previous work by comparing water-side (hydrodynamics and resulting diffusive boundary layer thickness, δ DBL) and sediment-side (oxygen consumption and resulting sediment oxic zone) approaches for evaluating diffusive sediment oxygen uptake rate (JO2) and δ DBL from microprofiles. Dissolved oxygen microprofile and current velocity data were analyzed using five common methods to estimate JO2 and δ DBL and to assess the robustness of the approaches. Comparable values for JO2 and δ DBL were obtained (agreement within 20%), and turbulence-induced variations in these parameters were uniformly characterized with the five methods. JO2 estimates based on water-side data were consistently higher (+1.8 mmol m–2 d–1 or 25% on average) and δ DBL estimates correspondingly lower (–0.4 mm or 35% on average) than those obtained using sediment-side data. This deviation may be attributed to definition of the sediment–water interface location, artifacts of the methods themselves, assumptions made on sediment properties, and/or variability in sediment oxygen-uptake processes. Our work emphasizes that sediment-side microprofile data may more accurately describe oxygen uptake at a particular location, whereas water-side data are representative of oxygen uptake over a broader sediment area. Regardless, our overall results show clearly that estimates of JO2 and δ DBL are not strongly dependent on the method chosen for analysis.