Kevin Hardy was 9 of 10 from the field with 18 points and nine rebounds for the Cowboys (3-2) who struggled from 3-point range (3 of 21) but shot 34 of 66 overall. Jamaya Burr added 12 points and five assists.
Michael Chinn's free throw pulled Southern within 63-54 with 3:55 left, but Guidry scored six of McNeese's eight straight points, putting the lead safely out of reach at 17.
Will Bailey and Thaddeus Showers led the Knights with 17 points each, Chinn added 14 points and Antonio Wright scored 10. Southern was 11 of 18 from 3-point range with Bailey leading the way on 5-of-7 shooting from distance.