Although ENSO and its global impacts through teleconnection have been known for decades, if and how the mean currents and mesoscale eddies in the Caribbean Sea are linked to ENSO remains an open question. Here, by analyzing satellite observations and an ocean reanalysis product, we found a close connection between mean currents, eddies in the Caribbean Sea and ENSO on interannual timescales. Strong El Niño events result in enhanced north-south sea surface height (SSH) differences and consequently stronger mean currents in the Caribbean Sea, and the opposite happens during La Niña events. The eddy kinetic energy (EKE) responses to ENSO via eddy-mean flow interaction, primarily through baroclinic instability, which releases the available potential energy stored in the mean currents to mesoscale eddies. Our results suggest some predictability of the mean currents and eddies in the Caribbean Sea, particularly during strong El Niño and La Niña events.