As the biopharmaceutical industry embraces continuous manufacturing there has been significant progress made in converting standard unit operations from batch to continuous. Cellulose-based depth filters are composed of a complex mix of cellulose fibers, inorganic filter aids, and resins that create wide pore size distributions and multiple modes of separation (e.g. size exclusion, adsorption). They are heavily used in batch processing due to their scalability, footprint, and cost-effectiveness, but have not yet been widely adopted in continuous processing and questions remain on their ability to provide consistent long-term performance. Here, we use a continuous secondary clarification application to investigate depth filter performance over long continuous operation. After initial offline screening, select depth filters were sterilized and connected inline with a CHO cell perfusion bioreactor and run for between one and nine days. We evaluate how fouling changes in continuous operation by fitting fouling models to the differential pressure data. Instantaneous filtrate quality is evaluated over run time and filter loading. Finally, we assess how flux and run duration impact filter capacities and process economics.