We examined horizontal spatial patterns of fish densities and zooplankton biomass at a fine spatial scale of 50 m across seasons before, during, and after an experimental lake destratification to determine how interacting trophic levels may respond to alteration of thermal stratification. We used semivariogram analysis to calculate maximum distances of autocorrelation for fish and zooplankton separately, and cross variograms to determine whether relationships between fish and zooplankton are positive or negative. Fish became more dispersed during the manipulation, likely due to a flight response with the loss of preferred cold water habitat. There were no changes in zooplankton horizontal distributions with mixing, but we detected seasonal trends in distribution and biomass. We detected positive relationships between fish densities and zooplankton biomass for portions of the year, but did not detect any negative relationships. There was no effect of lake mixing on spatial interactions between fish and zooplankton. Our results indicate that external factors, such as seasonal wind patterns, may drive whole-lake zooplankton distributions, and that fish respond horizontally to change in vertically structured processes, especially when reliant on depth-dependent variables such as cold water.