The Sea at Les Saintes-Maries-de-la-Mer depicts three boats floating on a calm sea with special attention to light and color. A fisherman is visible guiding the boat in the painting’s foreground. The painting’s high horizon places emphasis on the vast sea, with varying shades of blue and green standing out against the boats. Compared to the other dramatic seascape Van Gogh painted at Saintes-Maries, this one is calm and quaint, with nonthreatening waves rendered in blue and green. Horizontal lines close to the horizon represent calm seas, while swirling lines and whitecaps in the foreground suggest turbulence and nod to one of Van Gogh's favorite Japanese works, The Great Wave off Kanagawa.

The different shades of color Van Gogh used to depict the sea capture light’s interactions with water. He wrote that the "Mediterranean Sea is a mackerel color: in other words, changeable – you do not always know whether it is green or purple, you do not always know if it is blue, as the next moment the ever-changing sheen has assumed a pink or a gray tint." To contrast with the color of the water, Van Gogh signed his name in large red letters. Weeks after completing the painting, Van Gogh referred to boats in the ocean as a metaphor in a letter to his brother, Theo. Van Gogh wrote that artists like himself were "sailing on the high seas in our small and wretched boats, isolated on the great waves of time."