Knowledge gaps in the biosafety data of the nanocellulose (NC) for biomedical use through various routes of administration call for closer look at health and exposure evaluation. This work evaluated the potentially immunogenic contaminants levels, for example, endotoxin and (1,3)-beta-D-glucan, in four representative NCs, that is, wood-based NCs and bacterial cellulose (BC). The hot-water extracts were analyzed with ELISA assays, HPSEC-MALLS, GC, and NMR analysis. Varying levels of endotoxin and (1,3)-beta-D-glucan contaminats were found in these widely used NCs. Although the beta-(1,3)-D-glucan was not detected from the NMR spectra due to the small extract samples amount (2-7 mg), the anomerics and highly diastereotopic 6-CH2 signals may suggest the presence of beta-(1,4)-linkages with beta-(1,6) branching in the polysaccharides of NCs' hot-water extracts, which were otherwise not detectable in the enzymatic assay. In all, the article highlights the importance of monitoring various water-soluble potentially immunogenic contaminants in NC for biomedical use.