Matisse was visiting Paris when the Nazis invaded France in June 1940 but managed to make his way back to Nice. His son, Pierre, by then a gallery owner in New York, begged him to flee while he could. Matisse was about to embark for Brazil to escape the Occupation but changed his mind and remained in Nice. "It seemed to me as if I would be deserting," he wrote Pierre in September 1940. "If everyone who has any value leaves France, what remains of France?"

Matisse was shocked when he learned that his daughter Marguerite, who had been active in the French Resistance during World War II, was tortured (almost to death) by the Gestapo in a Rennes prison and sentenced to the Ravensbrück concentration camp in Germany. Marguerite managed to escape from the train to Ravensbrück, which was halted during an Allied air raid, and survived in the woods until she was rescued by fellow resisters. Matisse's student Rudolf Levy, however, was killed in the Auschwitz concentration camp in 1944.

While living in Vence, France, at the Villa Le Rêve in the 1940s, Matisse had three cats, Minouche, Coussi and La Puce, whom he fed pieces of brioche every morning. It is said that Coussi had an "M" for Matisse on his forehead.

In 1941, Monique Bourgeois responded to an ad placed by Matisse for a nurse. A platonic friendship developed between Matisse and Bourgeois. He discovered that she was an amateur artist and taught her about perspective. After Bourgeois left the position to join a convent in 1944, Matisse sometimes contacted her to request that she model for him.

Considered by some critics to be Matisse's masterpiece, The Dessert: Harmony in Red, was originally commissioned in blue, but Matisse was dissatisfied with the result and repainted the entire painting red. When it was delivered to the Russian collector Shchukin, he had no problem with the fact that his "Harmony in Blue" had become "Harmony in Red".

Between 1906 and 1917, Matisse lived and worked at the Hôtel Biron, an 18th-century mansion in Paris that had been subdivided into apartments. Among his neighbors were Jean Cocteau, Isadora Duncan and Auguste Rodin. Rodin eventually took over the entire house, which is now the famed Musée Rodin.

Diagnosed with abdominal cancer in 1941, Matisse underwent surgery that left him bedridden. Painting and sculpture had become physical challenges, so he turned to a new type of medium. With the help of his assistants, he began creating cut paper collages, or decoupage. He would cut sheets of paper, pre-painted with gouache, into shapes of varying colors and sizes, and arrange them to form lively compositions. Initially, these pieces were modest in size, but eventually grew into room-sized murals.

Besides his cats, Matisse adored doves, which he purchased from vendors along the Seine. The dove shape appears in many of his cut-outs and it was one of his birds on which the Spanish painter Picasso modeled his Dove of Peace (1949). In his last days, Matisse gifted his precious birds to Picasso.

The last work that Matisse completed before his death in 1954 was La Rosace, a circular stained-glass window that had been commissioned by future New York governor Nelson Rockefeller as a memorial for his mother, who was a great admirer of Matisse. "Nothing would have pleased mother more," Rockefeller wrote to a colleague. The window was installed at the Union Church of Pocantico Hills in Tarrytown, New York, where it remains today.