General anesthesia is usually induced with a combination of drugs. In addition to the hypnotic agent, such as propofol, opioids are often used due to their synergistic hypnotic and analgesic properties. However, the effects of opioids on the EEG changes and the clinical state of the patient during anesthesia are complex and hinder the interpretation of the EEG-based depth of anesthesia indexes. In this paper, a novel technology for separating the anesthetic effects of propofol and an ultrashort-acting opioid, remifentanil, using the spectral features of EEG is proposed. By applying a floating search method, a well-performing feature set is achieved to estimate the effects of propofol during induction of anesthesia and to classify whether or not remifentanil has been coadministered. It is shown that including the detection of the presence of opioids to the estimated effect of propofol significantly improves the determination of the clinical state of the patient, i.e., if the patient will respond to a painful stimulation.