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We wanted to verify the effect of combining multi‐echo (ME) functional magnetic resonance imaging (fMRI) with slice acceleration in simultaneous multi‐slice acquisition. The aim was to shed light on the benefits of multiple echoes for various acquisition settings, especially for levels of slice acceleration and flip angle. Whole‐brain ME fMRI data were obtained from 26 healthy volunteers (using three echoes; seven runs with slice acceleration 1, 4, 6, and 8; and two different flip angles for each of the first three acceleration factors) and processed as single‐echo (SE) data and ME data based on optimal combinations weighted by the contrast‐to‐noise ratio. Global metrics (temporal signal‐to‐noise ratio, signal‐to‐noise separation, number of active voxels, etc.) and local characteristics in regions of interest were used to evaluate SE and ME data. ME results outperformed SE results in all runs; the differences became more apparent for higher acceleration, where a significant decrease in data quality is observed. ME fMRI can improve the observed data quality metrics over SE fMRI for a wide range of accelerated fMRI acquisitions. [ABSTRACT FROM AUTHOR]