Fred Soper's "retirement" was an active one. Shortly after stepping down as Director of PAHO in January 1959, he embarked on a lengthy tour of Southeast Asia, accompanied by his wife Juliet, and Rockefeller colleague Robert B. Watson. From February to July 1959, they traveled in India, Thailand, Ceylon, Taiwan, and other countries, assessing malaria eradication programs for the Rockefeller Foundation. In November and December, Soper was in the Belgian Congo as a consultant to the International Cooperation Administration, assessing malaria control programs.

In the summer of 1960, Dr. Joseph Smadel asked Soper to establish the administrative machinery for a Cholera Research Laboratory being planned for Pakistan. Cholera had appeared in Thailand in 1958, after a relatively quiet decade, and spread rapidly through the country, threatening several of the countries that were members of the South East Asia Treaty Organization [SEATO]. The U. S. had sent a technical commission to Southeast Asia expecting to recommend collaboration in a cholera research program in Thailand. The commission found Pakistan, where cholera is permanently endemic, more suitable for long-term studies, and recommended basing the laboratory in East Pakistan (now Bangladesh). An agreement was drafted, providing U.S. collaboration (and funding) on the project for the first 3 years, and the U.S. had begun sending out personnel, materials, and lab equipment to set up the cholera lab at the public health institute in Dacca. Soper was to get the project up and running, and establish a basis for its long term administration. He arrived in Dacca in early 1961 and spent several months arranging for basic necessities such as typewriters and office furnishings, and wrestling with the local bureaucracy. These troubles, plus jurisdictional squabbles between American and Pakistani personnel, prompted Soper to resign from his position as of February 1962 and return to the U.S.

Soper continued to act as an advisor to PAHO, the U.S. Public Health Service, and the international health community. He also served on the executive committee and as Secretary of the Gorgas Memorial Institute, a tropical disease research facility founded in 1921. The Institute's research laboratory in Panama had done important tropical disease research for decades, but research had become much more expensive and, by the 1960s, the lab was in need of additional funding. Soper helped write funding proposals and recommended strengthening the lab's function as the central disease research facility in the region.

Following his wife's death in 1968, and with his own health declining, Soper gradually withdrew from active participation in international public health activities. He spent several years organizing his papers and writing his memoirs, working mainly at the National Library of Medicine in Bethesda, Maryland. He died on February 9, 1977 in Wichita, Kansas.