In this paper, a novel observer design is introduced to estimate the outputs of a Multi-Input-Multi-Output (MIMO) system. From the synthesis of state observer and Model-Free technique, the Model-Free Observer (MFO) is proposed to compensate for the un-modeled dynamics, modeling errors, and the system uncertainties. The developed output estimation technique using MFO is validated using real flights of a quadrotor UAV. Two flight-test missions are conducted to validate the proposed observer performance, in the fault free case as well as in the presence of actuator faults.