Covalent drugs may facilitate expansion of the druggable proteome through their potential to target proteins at sites that lack well-defined binding pockets generally targeted by non-covalent small molecules. The discovery of novel covalent compounds is aided by technologies such as chemoproteomic reactive cysteine profiling that can assess functional cysteine sites across the proteome to identify potential novel chemical matter targeting the cysteinome. Here, we present a strategy that enables cell-based compound screening to provide a comprehensive overview of putatively ligandable cysteine residues in the proteome. Making use of a 96-well-format and fragment pools for treatment, we applied this assay to profile ~250 fragments in live cells. We quantified almost 30,000 reactive cysteine sites originating from more than 9,200 proteins and identified ~750 strongly liganded cysteine sites (competition ratio (CR) >4; corrected p-value <0.05) in 640 proteins of which ~80% are considered undruggable so far. To validate the fragment pooling strategy, we compared the covalent CDK7 inhibitor THZ1 as single compound or as part of a fragment pool and observed congruent THZ1 cysteine site labeling on its primary target CDK7 and on potential off-targets. This pilot data indicates that we have developed a scalable live cell chemoproteomic platform to screen large compound libraries to expand the portrait of the potentially ligandable cysteinome.