Abstract Many studies in the literature optimise operation of individual components along the CCS process chain for base-load/design conditions. This fails to acknowledge the need for flexible operation of fossil CCS infrastructure in future low carbon energy systems, characterised by high shares of inflexible nuclear power and intermittent renewable power supply. In this environment CCS power stations are likely to be required to load-follow in order to balance the electricity grid. This results in extensive ramping and part-load operation as well as large variations in CO2 flows that are produced. Unless CO2 flow balancing techniques are deployed within the power stations, the CO2 transportation and storage (T&S) systems will need to accommodate these large fluctuations in feed-flows. This paper addresses an identified gap in the literature by exploring the issues associated with flexible operation of CO2 T&S systems, as well as options to overcome these issues. A particular focus is laid on the operational flexibility of injection wells as the potentially least flexible part of the system.