Macroporous silicon microcavities for detection of large biological molecules have been fabricated from highly doped n‐type silicon. Well‐defined controllable pore sizes up to 120 nm have been obtained by systematically optimizing the etching parameters. The dependence of the sensor sensitivity on pore size is discussed. Excellent infiltration inside these macroporous silicon microcavities is demonstrated using 60 nm diameter latex spheres and rabbit IgG (150 kDa; 1Da = 1 g mol–1). The sensing performance of the device is tested using a biotin/streptavidin couple, and protein concentration down to 1–2 μM (equivalent to 0.3 ng mm–2) could be detected. Simulations show that the sensitivity of the technique is currently approximately 1–2 % of a protein monolayer.