MOTIVATION: Models for analysing and making relevant biological inferences from massive amounts of complex single-cell transcriptomic data typically require several individual data-processing steps, each with their own set of hyperparameter choices. With deep generative models one can work directly with count data, make likelihood-based model comparison, learn a latent representation of the cells and capture more of the variability in different cell populations. RESULTS: We propose a novel method based on variational auto-encoders (VAEs) for analysis of single-cell RNA sequencing (scRNA-seq) data. It avoids data preprocessing by using raw count data as input and can robustly estimate the expected gene expression levels and a latent representation for each cell. We tested several count likelihood functions and a variant of the VAE that has a priori clustering in the latent space. We show for several scRNA-seq datasets that our method outperforms recently proposed scRNA-seq methods in clustering cells and that the resulting clusters reflect cell types. AVAILABILITY AND IMPLEMENTATION: Our method, called scVAE, is implemented in Python using the TensorFlow machine-learning library, and it is freely available at https://github.com/scvae/scvae. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.