Recent breakthroughs in genome-wide techniques, including chromatin immunoprecipitation ChIP followed by deep sequencing (ChIP-seq), have considerably expanded the usefulness of this small organism in basic research, including investigations into how proteins interact with DNA to regulate gene expression and on the role of histone post-translational modifications. To successfully sequence ChIP libraries, it is important to ensure that the sample fragments are within the acceptable size distribution range (100-800 bp). In this application note, we provide a step-by-step sample preparation protocol using the Covaris S220 that can be used by investigators looking to process whole body C. elegans extracts for ChIP-based applications.