The effects of sensory loss on central processing in various sensory systems have already been described. The olfactory system holds the special ability to be activated by a sensorimotor act, without the presentation of an odor. In this study, we investigated brain changes related to chronic peripheral smell loss. We included 11 anosmic patients (8f, 3m; mean age, 43.5 years) with smell loss after an infection of the upper respiratory tract (mean disease duration, 4.64 years) and 14 healthy controls (7f, 7m; mean age, 30.1 years) in a functional magnetic resonance imaging experiment with a sniffing paradigm. Data were analyzed using group-independent component analysis (ICA) and functional connectivity analysis. Our results revealed a spatially intact olfactory network in patients, whereas major aberrations due to peripheral loss were observed in functional connectivity through a variety of distributed brain areas. This is the first study to show the re-organization caused by the lack of peripheral input. The results of this study indicate that anosmic patients hold the ability to activate an olfaction-related functional network through the sensorimotor component of odor-perception (sniffing). The areas involved were not different from those that emerged in healthy controls. However, functional connectivity appears to be different between the two groups, with a decrease of functional connectivity in the brain in patients with chronic peripheral sensory loss. We further can conclude that the loss of the sense of smell may induce far-reaching effects in the whole brain, which lead to compensatory mechanisms from other sensory systems due to the close interconnectivity of the olfactory system with other functional networks.