Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world at an unprecedented rate. In the present study, 4 marine sulfated polysaccharides were screened for their inhibitory activity against SARS-CoV-2, including sea cucumber sulfated polysaccharide (SCSP), fucoidan from brown algae, iota-carrageenan from red algae, and chondroitin sulfate C from sharks (CS). Of them, SCSP, fucoidan, and carrageenan showed significant antiviral activities at concentrations of 3.90–500 μg mL⁻¹. SCSP exhibited the strongest inhibitory activity with IC₅₀ of 9.10 μg mL⁻¹. Furthermore, a test using pseudotype virus with S glycoprotein confirmed that SCSP could bind to the S glycoprotein to prevent SARS-CoV-2 host cell entry. The three antiviral polysaccharides could be employed to treat and prevent COVID-19.