AbstractA novel application of Multivariate Curve Resolution with Alternating Least Squares (MCR‐ALS) method for the background correction and for the resolution and quantitation of coeluted analyte mixtures in liquid chromatography with voltammetric detection is presented. The selected voltammetric technique for analyte detection was Linear Sweep Voltammetry (LSV), which provides richer multivariate information than the more widespread employed univariate amperometric detection. Use of other voltammetric detection techniques was also attempted but they gave much poorer results because of instrumental and software limitations concerning data acquisition times. The method is tested in the resolution and quantitation of mixtures of pyrocatechol, ascorbic acid and epinephrine coeluting mixtures. In spite of the extremely large background current contributions observed using this voltammetric technique, MCR‐ALS was shown to be able to model this background contribution satisfactory as well as to resolve and give good quantitative estimations of these three analyte in their mixtures. The proposed approach is recommended for resolution and quantitation of complex coeluted mixtures using liquid chromatography with voltammetric detection and also for fast initial screening of optimal potential when amperometric detection is preferred.