A bstract We analyse scalar leptoquark pair production at the LHC with predictions including t -channel lepton exchange contributions up to next-to-leading order (NLO) in QCD. In particular, we calculate NLO-QCD predictions for off-diagonal production channels, i.e. channels that involve two different leptoquark eigenstates and are driven solely by diagrams involving Standard Model leptons in the t -channel at leading order, as opposed to diagonal channels where a pair of the same leptoquark eigenstate is produced. We find that reliable theoretical predictions for both channels require NLO accuracy. The relative importance of the off-diagonal modes depends strongly on the considered scenario. In a generic model involving R 2 and S 3 leptoquarks, at large values of the Yukawa couplings off-diagonal contributions initiated by valence quarks can be up to an order of magnitude higher than the diagonal production. However, we also find that in phenomenologically viable scenarios addressing the flavour anomalies off-diagonal production is generally negligible, with a few exceptions of 10%–30% of the total rate depending on the treatment of the charm density in the proton.