During the manufacturing of therapeutic antibodies, disposable depth filters are used after affinity chromatography to remove haze and process-related impurities such as host cell proteins (HCP) and DNA known as critical quality attributes. The present study reports on the regeneration of depth filters allowing their reuse for at least 10 times while retaining sufficiently high clarification capacity. Three filter types were evaluated including standard cellulose-based and fully synthetic matrix materials using acidic or alkaline solutions in alternating cycles of loading and regeneration. Both alkaline and acidic solutions were effective, however, overall acidic regeneration of the filter material appeared superior for multiple use. This was especially evident for the silica-containing XOSP filter, where HCP and DNA were almost completely removed and remained low over 10 applications. Simultaneously preserved product quality indicated a high resistance of the filter matrix toward regeneration. These unexpected findings offer improved flexibility for available filter capacity in downstream processing along with ecologic advantages over the single use applications. Regarding the carbon footprint of the filtration process, calculated potential savings by a factor of four can be achieved, mainly accounting for reduced plastic waste. Therefore, depth filter reuse supports sustainability and carbon dioxide reduction during production processes.