Absence of fibrillin 2 (Fbn2), a non-collagenous bone protein, causes a connective tissue disorder called congenital contractural arachnodactyly (CCA) and has been associated with decreased bone mineral density. Nanoindentation and Raman microspectroscopy have been used to compare the mechanical and chemical properties of cortical bone from femora of Fbn2-/- deficient mice and their wild-type controls (Fbn2+/+). It was found that Fbn2-/- bones have significantly lower hardness and elastic modulus compared to Fbn2+/+ bones, especially in the mid-cortical section. The Raman analysis showed little difference with genotype except for a decrease in type-B carbonate substitution in the endosteal region of Fbn2-/- bones. The results indicate that Fbn2 plays a direct role in determining the mechanical properties of bone.