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Superman deals with losing his powers following exposure to red kryptonite.
Mr Mxyzptlk provides Lex Luthor with red kryptonite that renders Superman powerless. It takes Superman a while to work out what is responsible for his state, and in the meanwhile he is supported by Professor Hamilton, Starman, and Gangbuster. Starman and Gangbuster try to keep the streets safe in Superman's absence, while Hamilton builds a power suit for Superman to use in the interim.
Starman eventually determines that Luthor is responsible for Superman's loss of power, although strangely Hamilton can't detect any radiation in the red kyptonite Starman brings back.
It is only by tricking Luthor into revealing his source, namely Mxyzptlk, that Superman regains his powers and Mxyzptlk is once again banished to the fifth dimension.