This paper presents a CMOS optoelectronic lock-in amplifier (LIA) with semi-digital automatic phase alignment for optical sensing applications. The LIA incorporates a phase sensitive detection (PSD) channel and a phase alignment channel. A phase alignment loop generates the LIA reference clock, and automatically aligns the relative phase between the reference and the input signal through a phase interpolation providing unlimited (modulo 2π) phase shift. A finite state machine (FSM) is implemented in the digital domain to control the loop with low-power consumption and small chip area. The LIA is optimized to operate at a 50-kHz modulation frequency. The LIA is fully characterized optically and electrically, and measurement results are reported in this paper. The measured dynamic reserve and the sensitivity of the LIA are 35.37 dB and 296 mV/μW, respectively for a detection bandwidth of 50 Hz. The proposed LIA consumes an average power of 214 μW from a 1.8/3.3-V DC power supply.