Your cover letter is your chance to sell yourself to a company in ways that a resume cannot. The cover letter is the company's first impression of you as a potential employee, and listing a low GPA may seem counter-intuitive. However, if there are legitimate reasons for your low GPA -- whether you had personal problems during school or were involved in extracurricular activities -- the cover letter is an opportunity to explain your history and reassure your potential employer of your legitimacy as a job candidate.
Explain any family or personal situations that significantly affected your academic performance, if applicable. For example, if a loved one died during your time at school, and the death hindered your ability to do well in class, briefly discuss this fact on your cover letter. If you experienced a significant illness during school that resulted in many absences, explain the situation on your cover letter. Do not go into a lot of detail; explain that the situation took time emotionally, but you grew stronger from the experience.
Write the ways in which you changed during your time at school. If you allocated time poorly during your freshman or sophomore year, and your grades suffered as a result, write about the lessons you learned and how you changed. For example, say that you manage your time effectively because you saw your grades suffer previously. If you were not motivated to excel academically, explain that once you found the career path you wanted, you motivated yourself to succeed.
Demonstrate in your cover letter that you received higher grades in classes specific to your career, if applicable. Lower grades in courses required to fulfill basic degree requirements may bring down your GPA, but those grades are less important than the grades that related to your major. For example, your grades in philosophy and gym class could be Ds, but if you received As and Bs in your engineering classes, stress this fact on your cover letter.
Talk about extracurricular activities or networking situations that took time away from your studies. For example, if you are applying to a film production company, talk about the films and independent productions you worked on outside of school. Your prospective employer might understand that your grades slipped if you sought real-world experience in your selected profession.