Lee got the start Monday night against San Francisco after missing nine weeks because of an elbow strain.
Lee allowed six earned runs on 12 hits, lasting just 5 2/3 innings and 90 pitches. He added three strikeouts.
Brignac missed a month because of an ankle injury. Nieves also missed a month because of a quadriceps injury.
Gwynn batted .163 (16 for 98) with three extra-base hits and three RBIs.
Information from The Associated Press was used in this report.