In the United States Senate, he was a member of the U.S. Senate Committee on Foreign Relations until the end of his term on March 4, 1857. Fish became friends with President Franklin Pierce's Secretary of State William L. Marcy and Attorney General Caleb Cushing. He was a Republican for the latter part of his term and was part of a moderately anti-slavery faction. During the 1850s, the Republican Party replaced the Whig Party as the central party against the Democratic Party. By 1856, Fish privately considered himself a Whig although he knew that the Whig Party was no longer viable politically. Fish was a quiet Senator, rather than an orator, who liked to keep to himself. Fish often was in disagreement with Senator Sumner, who was firmly opposed to slavery and advocated equality for blacks. His policy was to vote for legislation on the side of "justice, economy, and public virtue." He strongly opposed the repeal of the Missouri Compromise. Fish often voted with the Free Soil faction and was strongly against the Kansas-Nebraska Bill. In February 1855, merchants represented by Moses H. Grinnell, criticized Fish's bill on immigration and maritime commerce. Fish's bill was designed to protect Irish and German immigrants who were dying on merchant ships during oceanic passage to America. The merchants believed that Fish's bill was oppressive to commercial interests over human interests.