The effects of confinement on the phase separation behavior of polymer-polymer mixtures have been frequently studied in morphologies such as thin films and rods, but little research exists with respect to the nanoscale droplet size regime. This paper addresses the phase separation of water-soluble polymers in submicron aerosol droplets. Atomized aerosol particles were prepared from aqueous solutions and dried using diffusion dryers. For poly(ethylene) glycol/dextran and poly(vinyl alcohol)/poly(4-styrene sulfonic acid) systems, small particles remain homogeneous, while larger particles undergo phase separation within a single particle. As the molecular weight of the polymers increases while a constant ratio between monomers of polymers A and B is maintained, phase separation occurs in smaller diameter particles. These trends are modeled using a combination of equations describing the nucleation of a new phase and the Flory-Huggins theory and provide qualitative agreement. These results provide insight into the phase separation of aqueous nanoscale polymer-polymer systems. Potential exists to make new polymer materials with unique properties due to the mixing of polymer combinations that normally undergo phase separation.