This deposition contains the X-ray diffraction data used for the PanDDA analysis of the fragment screen against the NSP3 macrodomain of SARS-CoV-2 described in Schuller et al. 2021 (DOI: 10.1126/sciadv.abf8711). A description of the files can be found in the "README" text file. The data in this deposition is from the fragment screen performed at UCSF using P43 crystals. The data from the fragment screen performed at UCSF using C2 crystals can be found here - https://zenodo.org/record/4716363 - in the zipped directory named "ucsf_nsp3_mac1_C2.zip".