An ensemble multivariate calibration algorithm, termed as MISEPLS, is proposed. In MISEPLS, when constructing a member model, the variables that have mutual information (MI) with the response less than a threshold are eliminated; thus, the modeling can be performed in a subset of original variables and some problems arising from multi-collinearity can be avoided. Through experiments on three near-infrared (NIR) spectroscopic datasets from the food industry, MISEPLS proves to be superior to the single-model full-spectrum PLS and MIPLS (PLS combined with MI-induced variable selection). MISEPLS can improve the accuracy and robustness of a calibration model, without increasing its complexity.