Large lakes may constitute a significant component of regional surface–atmosphere fluxes, but few efforts have been made to quantify these fluxes. Tracer-transport inverse models that infer the CO2 flux from the atmospheric concentration typically assume that the influence from large lakes is negligible. CO2 observations from a tall tower in Wisconsin segregated by wind direction suggested a CO2 signature from Lake Superior. To further investigate this difference, source–receptor influence functions derived using a mesoscale transport model were applied and results revealed that air masses sampled by the tower have a transit time over the lake, primarily in winter when the total lake influence on the tower can exceed 20% of the total influence of the regional domain. When the influence functions were convolved with air–lake fluxes estimated from a physical–biogeochemical lake model, the overall total contribution of lake fluxes to the tall tower CO2 were mostly negligible, but potentially detectable in certain periods of fall and winter when lake carbon exchange can be strong and land carbon efflux weak. These findings suggest that large oligotrophic lakes would not significantly influence inverse models that incorporate tall tower CO2.