In August 2006, Mellor signed a three-year contract with Football League Championship club Preston North End for an undisclosed fee, thought to be in the region of £1.5m. Manager Paul Simpson said, ""Neil is a goalscorer and hopefully that will continue to be the case. He is a tremendous signing. He has had his injury problems but we are happy he is over those and it's just a case now of building up his fitness levels."" Another knee injury suffered in a pre-season friendly against Bolton Wanderers required more surgery and delayed Mellor's debut for Preston. Mellor finally got his first goal for Preston in the 3–1 victory over Southampton in March 2007. Out of favour under the Paul Simpson managerial era, Mellor had to prove himself over again to new P.N.E boss Alan Irvine. Under Irvine, Mellor finally got going and scored nine goals under him after Christmas 2007. Mellor again showed his panache for the 30-yard volley on 30 July 2008 by scoring in similar fashion for Preston North End in their friendly against Motherwell at Fir Park, which earned a 1–1 draw for Preston. During pre-season 2008–09 Mellor scored eight goals.