The reigning MLS champions lost eight of their first 13 league matches of the 2012 campaign and Arena believes that Donovan's stint at Everton and Keane's spell with Aston Villa made it difficult for the pair to get accustomed to each other's games during pre-season.
"We made a big mistake in having players loaned out right until the start of the season," Arena said.
"Although they played together at the end of last year, they still needed time together and we started with a group of players who hadn't had a preseason together - which was a major mistake.
"I accept the responsibility for that. Now we're building into the second half of the season, they're much more familiar with each other, and they're playing better."
More recently though, the Galaxy have improved their form with seven wins from their last nine outings, which has seen Donovan and Keane score 13 of the teams 23 goals during that time.