Abstract CO is commonly used as a tracer of the total gas mass in both the interstellar medium and in protoplanetary disks. Recently, there has been much debate about the utility of CO as a mass tracer in disks. Observations of CO in protoplanetary disks reveal a range of CO abundances, with measurements of low CO to dust mass ratios in numerous systems. One possibility is that carbon is removed from CO via chemistry. However, the full range of physical conditions conducive to this chemical reprocessing is not well understood. We perform a systematic survey of the time dependent chemistry in protoplanetary disks for 198 models with a range of physical conditions. We vary dust grain size distribution, temperature, comic-ray and X-ray ionization rates, disk mass, and initial water abundance, detailing what physical conditions are necessary to activate the various CO depletion mechanisms in the warm molecular layer. We focus our analysis on the warm molecular layer in two regions: the outer disk (100 au) well outside the CO snowline and the inner disk (19 au) just inside the midplane CO snowline. After 1 Myr, we find that the majority of models have a CO abundance relative to H2 less than 10−4 in the outer disk, while an abundance less than 10−5 requires the presence of cosmic-rays. Inside the CO snowline, significant depletion of CO only occurs in models with a high cosmic-ray rate. If cosmic-rays are not present in young disks, it is difficult to chemically remove carbon from CO. Additionally, removing water prior to CO depletion impedes the chemical processing of CO. Chemical processing alone cannot explain current observations of low CO abundances. Other mechanisms must also be involved.