SARS-CoV-2 has been reported as one of the deadliest viruses in history. Currently, few antiviral treatments are available to prevent SARS-CoV-2 transmission and progression to severe disease, especially in low-income countries. Natural products stand as a potential source of bioactive compounds. The antiviral activity against SARS-CoV-2 of Chlorella vulgaris microalgae has been demonstrated, however, the nature of its antiviral compounds remains unexplored. In this study, the in vitro antiviral activity of extracts and fractions derived from C. vulgaris algae dry powder, produced as a food supplement, was assessed. To determine the in vitro antiviral activity Vero cells were incubated with different concentrations of extracts and fractions against 100 TCID50/ml of SARS-CoV-2 variants. C. vulgaris ethanolic and diethyl ether extracts showed no cytopathic effect in 100% of the replicates. Fractions F11, F12, and F21, composed of high-weight polysaccharides and small proteins, partially protect against viral infection. These results suggest that polysaccharides, proteins, and pigments are related to antiviral activity.