Direct measurements of a depletion interaction between silica surfaces immersed in binary mixtures of non-adsorbing sodium poly(styrene sulfonate) have been made with an atomic force microscope. Variations in the secondary minimum depletion interaction as a function of binary mixture composition were recorded for a number of polymer molecular weights. The position and depth of the minimum in the force data was seen to depend on both the binary mixture composition and the choice of polymer molecular weights used in the mixture. For binary mixtures containing a low molecular weight polymer at a concentration near to or below the chain overlap concentration (C*) the position and depth of the minimum was seen to depend strongly on the properties of this low molecular weight component. This is consistent with previous theory predictions that depletion interactions in binary polymer mixtures will be controlled by the smaller component which can reside within the depletion layer of the higher molecular weight component.