In an effort to flee Nazi Germany, 907 refugees sailed from Hamburg on May 15, 1939 on the S.S. St. Louis and reached Havana, Cuba, on May 27, 1939. Arrangements for the voyage were organized independently by the Hamburg-American Line, without the involvement of any Jewish organizations. After the Cuban government refused to honor the refugees' accredited landing documents, however, JDC became involved in negotiations with the Cuban government. These discussions unfortunately failed, as did efforts by JDC to find a haven for the desperate refugees elsewhere in the Americas. After 12 days of waiting, the St. Louis sadly headed back to Hamburg with all of its passengers.

While the St. Louis was on the high seas, JDC, in close cooperation with other groups, negotiated with the governments of Holland, Belgium, England, and France to accept the refugees until homes in other countries could be found. JDC posted a cash guarantee of $500,000 ($500 per refugee) in order to make the arrangement feasible and to cover upkeep costs wherever necessary.

In England, JDC continued to support the last of the St. Louis refugees until 1948, but in France, Belgium, and Holland, the Nazi occupation reduced the channels of outside aid and ultimately brought those routes to a standstill. After the occupation of France, some St. Louis refugees escaped to Switzerland. But there were others who had returned to Europe on that fateful ship who ultimately met a tragic end in concentration camps.

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