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The 2012 NFL schedule for the 49ers is posted below.
| WK | DATE | OPPONENT | TIME (ET) |
| 1 | Sun, Sep 9 | at Green Bay | 4:15 PM |
| 2 | Sun, Sep 16 | Detroit | 8:20 PM |
| 3 | Sun, Sep 23 | at Minnesota | 1:00 PM |
| 4 | Sun, Sep 30 | at NY Jets | 1:00 PM |
| 5 | Sun, Oct 7 | Buffalo | 4:15 PM |
| 6 | Sun, Oct 14 | NY Giants | 4:15 PM |
| 7 | Thu, Oct 18 | Seattle | 8:20 PM |
| 8 | Mon, Oct 29 | at Arizona | 8:30 PM |
| 10 | Sun, Nov 11 | St. Louis | 4:15 PM |
| 11 | Mon, Nov 19 | Chicago | 8:30 PM |
| 12 | Sun, Nov 25 | at New Orleans | 4:15 PM |
| 13 | Sun, Dec 2 | at St. Louis | 1:00 PM |
| 14 | Sun, Dec 9 | Miami | 4:05 PM |
| 15 | Sun, Dec 16 | at New England | 8:20 PM |
| 16 | Sun, Dec 23 | at Seattle | 4:15 PM |
| 17 | Sun, Dec 30 | Arizona | 4:15 PM |
