As social beings, humans harbor an evolved capacity for loneliness—perceived social isolation. Feelings of loneliness are associated with aberrant affective and social processing, as well as deleterious physiological dysregulation. We investigated how loneliness affects spontaneous facial mimicry (SFM), an interpersonal resonance mechanism involved in social connection and emotional contagion. We used facial electromyography (fEMG) to measure activity of the zygomaticus major (“smiling muscle”) and corrugator supercilii (“frowning muscle”) while participants viewed emotional stimuli, such as video clips of actors expressing anger, fear, sadness, or joy, and emotional IAPS images. We also measured self-reported loneliness, depression, and extraversion levels. Evidence for SFM was found in greater fEMG activity of the zygomaticus and corrugator to positive and negative emotions, respectively. However, individuals reporting higher levels of loneliness lacked SFM for expressions of joy. Loneliness did not affect deliberate mimicry activity to the same expressions, or spontaneous reactions to positive, negative, or neutral IAPS images. Depression and extraversion did not predict any differences in fEMG responses. We argue that impaired automaticity of “smiling back” at another—a faulty interpersonal resonance response—represents a pervasive behavioral mechanism that likely contributes to negative social and emotional consequences of loneliness and may facilitate loneliness contagion.