Systems and methods for estimating Signal-to-Noise Ratio (SNR) for Multi-User Multiple-Input and Multiple-Output (MU-MIMO) based on channel orthogonality. In some embodiments, a method performed by a radio access node includes obtaining a SU-MIMO signal quality measurement for at least a first user and an additional user; obtaining an indication of orthogonality between a channel of the first user and a channel of the additional user; and estimating a MU-MIMO signal quality measurement for the first user as if the first user and the additional user are paired with each other for a potential MU-MIMO transmission based on the SU-MIMO signal quality measurements and the indication of orthogonality. In this way, a computational complexity for the SINR estimation of MU-MIMO users can be greatly reduced. This may enable a large number of user pairing alternatives to be evaluated in practical wireless systems to achieve improved MU-MIMO performance.