Locally low-rank (LLR) denoising of functional magnetic resonance imaging (fMRI) time series image data is extended to multi-echo (ME) data. The proposed method extends the capabilities of non-physiologic noise suppression beyond single-echo applications with a dedicated ME algorithm. Following an institutional review board (IRB) approved protocol, resting-state fMRI data were acquired in 7 healthy subjects. A compact 3T scanner enabled whole-brain acquisition of multiband ME fMRI data at high spatial resolution (1.4 × 1.4 × 2.8 mm 3 ) with a 1810 ms repetition time (TR). Image data were denoised with ME-LLR preceding functional processing. The results of connectivity maps generated from denoised data were compared with maps generated with equivalent processing of non-denoised images. To assess ME-LLR as a method to reduce scan time, comparisons were made between maps computed from image data with full and retrospectively truncated durations. Assessments were completed with seed-based connectivity analyses using echo-combined image data. In a feasibility assessment, nondenoised and denoised full-duration echo-combined data were equivalently processed with independent component analysis (ICA) and compared. ME-LLR denoising yielded strengthened resting-state network connectivity maps after nuisance regression and seed-based connectivity analysis. In assessing ME-LLR as a scan reduction mechanism, maps generated from denoised data at half scan time showed comparable quality with maps generated from full-duration, non-denoised data, at both single subject and group levels. ME-LLR substantially increased temporal signal-to-noise ratio (tSNR) for image data respective to each individual echo and for image data after nuisance regression. Among echo-specific image volumes, increases in tSNR yielded by ME-LLR were most pronounced for image data with the longest echo time and thereby lowest SNR. ICA showed resting-state networks consistently identified between non-denoised and denoised data, with clearer demarcation of networks for ME-LLR. ME-LLR is demonstrated to suppress non-physiologic noise, enhance functional connectivity map quality, and could potentially facilitate scan time reduction in ME-fMRI.