Crossflow microfiltration and ultrafiltration are widely used in membrane bioreactors for wastewater treatment and applications in the food, biotechnology and process industries. Membrane fouling is an endemic problem in these operations that can be mitigated by backwashing and intermittent relaxation of the pressure or flux. Intermittent relaxation offers advantages relative to backwashing since it does not alter the membrane morphology or damage susceptible membranes, provides a more uniform removal of the foulant cake layer, and is potentially more energy-efficient. This paper reports a study of intermittent relaxation to mitigate fouling under both constant flux and constant pressure operation using a regenerated cellulose flat sheet ultrafiltration membrane (MWCO 30 kDa) and two model foulants: colloidal silica that is completely rejected and highly compressible and metastable; and, humic acid that is partially rejected and thereby can cause internal pore fouling and is relatively incompressible. Intermittent relaxation more effectively mitigated humic acid fouling owing to the compressibility and metastability of colloidal silica. An optimum relaxation frequency exists owing to the counterbalancing effects between increasing the permeation flux and reducing the time for permeation, which is determined for both constant flux and constant pressure operation. Design heuristics are advanced for the operation of intermittent relaxation.