A processor/endpoint communication coupling configuration system includes a plurality of processing subsystems coupled to a multi-endpoint adapter device by a plurality of communication couplings included on at least one hardware subsystem. A communication coupling configuration engine identifies each at least one hardware subsystem, determines at least one communication coupling configuration capability of the plurality of communication couplings, and determines at least one first multi-endpoint adapter device capability of the multi-endpoint adapter device. The communication coupling configuration engine then configures the plurality of communication couplings based on the at least one hardware subsystem, the at least one communication configuration capability, and the at least one first multi-endpoint adapter device capability in order to provide at least one communication resource between at least one of the plurality of processing subsystems and at least one endpoint on the first multi-endpoint adapter device.