A reliable datagram service is implemented with a source and destination resource (SDR). Source SDR resources, at a source device, multiplex units of work produced by at least one source application instance (AI) into a serial unit of work stream having units of work in a defined order and transmit the serial unit of work stream over a communication services/fabric. Destination SDR resources, at a destination device, receive the serial unit of work stream, demultiplex the serial unit of work stream into units of work provided to at least one destination AI, and provide a negative acknowledgement (NAK) for a unit of work received ahead of its defined order.