Multi-stage back pressure regulators are disclosed herein. In one embodiment, a multi-stage back pressure regulator includes a first stage and a second stage downstream from the first stage. The first stage includes a gas-charged regulator device arranged to receive a fluid at an inlet, and the second stage includes a spring-loaded regulator device having an outlet in fluid communication with the inlet. The gas-charged regulator and the spring-loaded regulator are configured to control inlet pressure to the back pressure regulator and maximum differential pressures across the first and second stages.