The strength of chromatography lies in the ability of fine-tuning recovery for specific target components or fractions of interest. A downside of industrial chromatography is the need to dilute streams, as it is often applied today. This article challenges the conventional low concentration of input streams and investigates size exclusion chromatography at concentrated streams of high viscosity. Chromatographic operation with concentrated streams leads to an increased pressure drop over the column and decreased mass transfer kinetics, but also lower volumes compared to diluted streams. The objective of this research was to investigate separation performance and system dimensions as a function of viscosity for food type streams, in scenarios where viscosity is not caused by target components. Disadvantages due to increased stream volume with decreasing concentration and benefits due to decreased viscosity were evaluated, aiming to find minimal column volume. Separation performance was evaluated for a range of target components in a preparative lab-scale system using a size exclusion resin and mobile phase viscosities in the range of 1.2–8.7 mPa⋅s. Mobile phases were viscosified through addition of sucrose, glycerol, or dextran. Change in mass transfer resistance, measured via van Deemter curves, was related to the change in diffusivity through viscosity. The analysis of different viscosifying agents emphasized the influence of viscosity inside the pores, rather than viscosity of the bulk phase. The viscosity inside the pores was calculated via the partition coefficient of each viscosifying agent. Based on the slopes of van Deemter curves, column dimensions were calculated for different scenarios, assuming a non-compressible stationary phase. Column volume remained constant with stream dilution from 8.7 mPa⋅s down to about 2.5 mPa⋅s. However, at the same time column geometry changed to thinner and longer columns with decreasing viscosity, in order to accommodate throughput and pressure drop. When diluting to even lower viscosities, column volume increased, since stream viscosity is less sensitive to stream concentration at the low viscosity range. These results are relevant to a wide range of industries utilizing weak interaction chromatography, especially those where the main driver of process development is cost reduction and where a trade-off between purity, yield, and costs has to be made.