Shooting Isle of the Dead proved frustrating for the members of the Lewton unit. On July 22, 1944, the ninth day of shooting, Boris Karloff's old back injury flared up so badly that the star needed surgery. The film went into an indefinite hiatus. When Karloff was ready for work again, key cast members Skelton Knaggs and Rose Hobart were busy on other projects. The entire film The Body Snatcher was scripted and shot before the cast for Isle of the Dead reassembled to resume shooting on December 1, 1944.

During the long hiatus, Lewton rewrote the entire script. Among other changes, he shifted relationships among major characters. Originally General Pherides (Boris Karloff) was estranged father to Thea (Ellen Drew), Mrs. St. Aubyn (Katherine Emery) was Mr. St. Aubyn's (Alan Napier) daughter rather than wife, and Oliver (Marc Cramer) had a different love interest named Cathy (Rose Hobart) instead of Thea. Lewton streamlined the cast in his rewrite, eliminating the role of Cathy even though some of her scenes had already been shot. These changes complicated everything as some material shot before Karloff’s injury no longer made sense owing to various script revisions. Editor Lyle Boyer probably deserves more credit for the film's effectiveness than he gets in the critical literature for patching the pieces together, especially when considering that this was Boyer's first feature film as editor.

Lewton shared his despairing views on the production in letters to his mother and sister in New York. As reshooting began, he wrote: “Isle of the Dead, which we are shooting now, is a complete mess. I’m thankful that it is my last horror picture and, at the same time, sorry that I couldn't depart that field with a final success.” Later, he wrote: “Isle of the Dead, which we just finished shooting, looks pretty hopeless.” Then he offered his last words on the film after post-production concluded: