AbstractSingle-cell RNA-sequencing has become a widely used, powerful approach for studying cell populations. However, these methods often generate multiplet artifacts, where two or more cells receive the same barcode, resulting in a hybrid transcriptome. In most experiments, multiplets account for several percent of transcriptomes and can confound downstream data analysis. Here, we present Scrublet (Single-Cell Remover of Doublets), a framework for predicting the impact of multiplets in a given analysis and identifying problematic multiplets. Scrublet avoids the need for expert knowledge or cell clustering by simulating multiplets from the data and building a nearest neighbor classifier. To demonstrate the utility of this approach, we test Scrublet on several datasets that include independent knowledge of cell multiplets.