| # | County | State | Population | Change since 2020 | Unemployment rate |
| 1 | O'Brien County | Iowa | 14,260 | 0.6 % | 2.7 % |
| 2 | Oakland County | Michigan | 1,296,888 | 1.8 % | 3.9 % |
| 3 | Obion County | Tennessee | 30,261 | -1.7 % | 3.7 % |
| 4 | Ocean County | New Jersey | 666,434 | 4.6 % | 5.3 % |
| 5 | Oceana County | Michigan | 27,014 | 1.3 % | 7.4 % |
| 6 | Ochiltree County | Texas | 9,717 | -3.0 % | 3.2 % |
| 7 | Oconee County | South Carolina | 82,475 | 4.9 % | 4.2 % |
| 8 | Oconee County | Georgia | 44,751 | 7.0 % | 2.7 % |
| 9 | Oconto County | Wisconsin | 40,037 | 2.8 % | 3.4 % |
| 10 | Ogemaw County | Michigan | 20,985 | 1.0 % | 8.9 % |
| 11 | Oglala Lakota County | South Dakota | 13,360 | -2.3 % | 5.2 % |
| 12 | Ogle County | Illinois | 51,345 | -1.0 % | 4.7 % |
| 13 | Oglethorpe County | Georgia | 16,172 | 9.1 % | 2.9 % |
| 14 | Ohio County | West Virginia | 41,090 | -3.1 % | 4.2 % |
| 15 | Ohio County | Kentucky | 23,933 | 0.7 % | 5.6 % |
| 16 | Ohio County | Indiana | 5,996 | 1.1 % | 3.5 % |
| 17 | Okaloosa County | Florida | 220,483 | 4.2 % | 3.8 % |
| 18 | Okanogan County | Washington | 44,942 | 6.8 % | 5.2 % |
| 19 | Okeechobee County | Florida | 42,369 | 6.9 % | 4.6 % |
| 20 | Okfuskee County | Oklahoma | 11,364 | 0.5 % | 4.1 % |
| 21 | Oklahoma County | Oklahoma | 816,490 | 2.5 % | 3.4 % |
| 22 | Okmulgee County | Oklahoma | 37,084 | 1.0 % | 4.2 % |
| 23 | Oktibbeha County | Mississippi | 51,965 | 0.4 % | 4.1 % |
| 24 | Oldham County | Kentucky | 70,525 | 4.3 % | 3.9 % |
| 25 | Oldham County | Texas | 1,823 | 3.7 % | 3.3 % |
| 26 | Oliver County | North Dakota | 1,882 | 0.4 % | 3.7 % |
| 27 | Olmsted County | Minnesota | 166,424 | 2.2 % | 3.1 % |
| 28 | Oneida County | New York | 228,347 | -1.6 % | 3.9 % |
| 29 | Oneida County | Wisconsin | 38,175 | 0.9 % | 3.4 % |
| 30 | Oneida County | Idaho | 4,976 | 9.0 % | 2.9 % |
| 31 | Onondaga County | New York | 469,812 | -1.4 % | 3.6 % |
| 32 | Onslow County | North Carolina | 212,954 | 4.1 % | 4.0 % |
| 33 | Ontario County | New York | 113,012 | 0.5 % | 3.4 % |
| 34 | Ontonagon County | Michigan | 5,824 | 0.2 % | 7.6 % |
| 35 | Orange County | California | 3,170,435 | -0.5 % | 4.1 % |
| 36 | Orange County | Florida | 1,533,646 | 7.3 % | 3.8 % |
| 37 | Orange County | New York | 411,767 | 2.6 % | 3.9 % |
| 38 | Orange County | North Carolina | 152,877 | 2.8 % | 3.3 % |
| 39 | Orange County | Texas | 86,115 | 1.5 % | 4.6 % |
| 40 | Orange County | Virginia | 38,986 | 7.7 % | 3.4 % |
| 41 | Orange County | Vermont | 30,050 | 2.6 % | 2.9 % |
| 42 | Orange County | Indiana | 19,824 | -0.2 % | 3.7 % |
| 43 | Orangeburg County | South Carolina | 83,129 | -1.3 % | 6.4 % |
| 44 | Oregon County | Missouri | 8,699 | 0.7 % | 4.6 % |
| 45 | Orleans County | New York | 39,686 | -1.8 % | 4.1 % |
| 46 | Orleans County | Vermont | 27,726 | 1.2 % | 4.3 % |
| 47 | Orleans Parish | Louisiana | 362,701 | -5.6 % | 4.8 % |
| 48 | Osage County | Oklahoma | 46,495 | 1.5 % | 3.8 % |
| 49 | Osage County | Kansas | 15,737 | -0.2 % | 3.7 % |
| 50 | Osage County | Missouri | 13,478 | 1.6 % | 3.1 % |
| 51 | Osborne County | Kansas | 3,353 | -4.1 % | 3.6 % |
| 52 | Osceola County | Florida | 468,058 | 20.4 % | 4.1 % |
| 53 | Osceola County | Michigan | 23,484 | 2.6 % | 7.1 % |
| 54 | Osceola County | Iowa | 6,036 | -2.5 % | 2.3 % |
| 55 | Oscoda County | Michigan | 8,596 | 4.6 % | 11.0 % |
| 56 | Oswego County | New York | 118,305 | 0.6 % | 4.3 % |
| 57 | Otero County | New Mexico | 69,711 | 2.8 % | 4.4 % |
| 58 | Otero County | Colorado | 17,991 | -3.7 % | 5.4 % |
| 59 | Otoe County | Nebraska | 16,591 | 4.3 % | 2.8 % |
| 60 | Otsego County | New York | 60,524 | 3.4 % | 4.3 % |
| 61 | Otsego County | Michigan | 26,083 | 4.0 % | 5.9 % |
| 62 | Ottawa County | Michigan | 306,235 | 3.4 % | 4.2 % |
| 63 | Ottawa County | Ohio | 39,692 | -1.7 % | 6.5 % |
| 64 | Ottawa County | Oklahoma | 30,404 | 0.4 % | 3.7 % |
| 65 | Ottawa County | Kansas | 5,853 | 2.1 % | 3.2 % |
| 66 | Otter Tail County | Minnesota | 60,884 | 1.4 % | 4.6 % |
| 67 | Ouachita County | Arkansas | 21,684 | -4.3 % | 5.0 % |
| 68 | Ouachita Parish | Louisiana | 157,874 | -1.6 % | 4.5 % |
| 69 | Ouray County | Colorado | 5,197 | 6.5 % | 4.3 % |
| 70 | Outagamie County | Wisconsin | 195,390 | 2.5 % | 2.9 % |
| 71 | Overton County | Tennessee | 23,551 | 4.6 % | 3.5 % |
| 72 | Owen County | Indiana | 21,851 | 2.4 % | 3.7 % |
| 73 | Owen County | Kentucky | 11,435 | 1.5 % | 4.4 % |
| 74 | Owsley County | Kentucky | 3,928 | -3.1 % | 5.7 % |
| 75 | Owyhee County | Idaho | 12,748 | 7.0 % | 4.0 % |
| 76 | Oxford County | Maine | 60,039 | 4.0 % | 3.8 % |
| 77 | Ozark County | Missouri | 9,090 | 6.3 % | 6.3 % |
| 78 | Ozaukee County | Wisconsin | 93,956 | 2.7 % | 2.8 % |