A system, method, and software for optimizing the commingling of well fluids from a plurality of producing subsea wells. The mixing temperature and water content in each header of a collection manifold are calculated for each subsea well and header combinations, responsive to data from sensors at the collection manifold. Combinations with conditions outside operational limits are then discarded. Remaining combinations are ranked based on predetermined optimization criteria. The ranked combinations are provided for the operator for optimizing flow properties and well fluid production. The calculations can restart with new, real-time sensed values from the subsea collection manifold.