Wood, trying to stay off the disabled list and make the opening-day roster as a reliever, gave up a two-run homer to Kendry Morales after the Angels tied it at 1. In his one inning, Wood yielded three hits while striking out one.
"He wasn't as sharp today, obviously," Cubs manager Lou Piniella said. "The fastball didn't have the life of the last time. We'll see how he feels (Monday)."
Wood, who rehabbed this winter from a shoulder injury, strained his right triceps March 11 and didn't pitch again until Friday. For the spring, Wood has thrown five innings, giving up seven hits, seven runs and two homers. The Cubs hope to convert him from a starter to a one-inning reliever this year.
The team hasn't decided whether Wood will open the season on the active roster or if he needs more time to build up arm strength.
Santana retired his first 12 batters before Cliff Floyd led off the fifth inning with a home run, his second of the spring.
Santana pitched 6 1-3 innings, giving up four hits and one run. He walked one and struck out one.
Lilly worked six scoreless innings for the Cubs. He allowed four hits while walking one and striking out four.
In the Angels' three-run seventh, Erick Aybar singled with one out against Wood. A single by Howie Kendrick put runners on first and third. An RBI groundout by Jose Molina scored Aybar. Morales homered down the right-field line.
The Cubs scored in the eighth when Floyd walked with the bases loaded.