Fibromodulin is a keratan-sulfate small leucine-rich proteoglycan (SLRP) regulating collagen I and II fibril formation. In vivo studies suggest that, alongside decorin, fibromodulin plays an important role in the maintenance of mature tissues. To characterize fibromodulin/decorin differences in binding to type I and II collagen, we tested the collagen CNBr peptides in solid-phase assays. Only one peptide from collagen II and several peptides from collagen I interacted with fibromodulin, pointing to multiple binding sites in the collagen I molecule. By Scatchard-type analysis, the fibromodulin molecule showed only one class of binding sites for collagen I and both low and high affinity (classes of) binding sites for collagen II. Lys/Hyl residues in both collagens are essential for the interaction. Fibril formation assays showed the concomitant presence of fibromodulin and decorin in fibrils and a cumulative inhibitory effect. In solid-phase assays decorin seems to inhibit fibromodulin binding, whereas the contrary does not occur. We found fibromodulin and decorin have similarities and differences that may represent the biochemical basis of redundancy in SLRP function with compensation between different (classes of) SLRPs.