Small, low molecular weight, non-enzymatic compounds have been linked to the early stages of brown rot decay as the enzymes involved with holocellulose degradation are too large to penetrate the S3 layer of intact wood cells. We investigated the most notable of these compounds, i.e. hydrogen peroxide, iron, and oxalic acid. The former two are involved in the Fenton reaction in which they react to form hydroxyl radicals, which cause an accelerated depolymerization in cotton cellulose. We found the same reaction to be caused by both iron Fe3+ and Fe2+. A 10 mM oxalic acid solution showed significant depolymerization effect on cotton cellulose. An oxalic acid/sodium oxalate buffered pH gradient had an inhibitory effect on the reduction of cellulose polymers at increased pH values. The organic iron chelator, EDTA, was found to promote depolymerization of cellulose in combination with Fenton’s reagents, but inhibited the effect of oxalic acid in the absence of iron and hydrogen peroxide. Manganese was tested to see if metals other than iron could generate a significant impact on the degree of polymerization (DP) in cotton cellulose. Depolymerizing properties comparable to iron were seen. The results confirm that low molecular weight metabolites are capable of depolymerizing cellulose and suggest an importance of these mechanisms during incipient decay by brown rot fungi.